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Cancer Immunotherapy is the use of the immune system to reject cancer. The main premise is stimulating the patient's immune system to attack the malignant tumor cells that are responsible for the disease.
This is an incorrect generalisation, and as such should not be part of the opening paragraph, if TK inhibitors and radioimmunotherapy are classed as part of cancer immunotherapy, rather than as targeted therapy. Whilst immune stimulation is a strategy, this is emphatically not the technique used by most of the commercial monoclonals used today eg the tyrosine kinase inhibitors such as Herceptin, Cetuximab, which interfere with the ErbB family. Nor is it the mode of action of the radioconjugates such as Zevalin, or Bexxar. Jellytussle 20:12, 11 May 2006 (UTC)
It is generally accecpted that cancer immunotherapy refers to the use of monoclonal antibodies in the treatment of cancer, so I have removed references to IL-2, artificial T cell receptors, Imiquimod and vaccines. They would be more approiately placed in an article on immune modification or immune modifiers.
The problem is that this makes the opening paragraph even more irrelevant. I think it is instructive to look at a respectable and authoritative source for a good summary of definitions. This is taken from the Cancer Research UK website:
"Immunotherapy
* It can stop the cancer from growing by stopping other essential 'growth factors' from sticking to it. * It can 'tag' the cancer for destruction by the immune system. * If cancer drugs or radioactive particles are attached to the antibody, it can deliver them directly to the cancer cell without harming the rest of your body. * An enzyme (a type of protein that can promote chemical reactions) can be attached to an antibody, and then given to a patient along with a chemical that can be turned into a powerful drug by the enzyme. This directs the drug to the cancer, and minimise side effects. This process is known as Antibody-directed Enzyme/Pro-drug Therapy (ADEPT).
Jellytussle 23:47, 30 May 2006 (UTC)
Yes, Immunotherapy is a very ambigious name, as many immunological-based techniques are employed in cancer treatment. Monoclonal antibody therapy is a very distinct and high profile treatment, so it requires its own article. Maybe we should rename this article with something more specific and use "Immunotherapy" as an all encompasing aricle on immunological-based treatments in cancer. -- Cellpath 01:17, 3 June 2006 (UTC)
Other kinds of tumor cells display cell surface receptors that are rare or absent on the surfaces of healthy cells, and which are responsible for activating cellular signaling pathways that cause the unregulated growth and division of the tumor cell. Examples include ErbB2, a constitutively active cell surface receptor that is produced at abnormally high levels on the surface of appromimately 30% of breast cancer tumor cells. Such breast cancer is known a Her-2 positive breast cancer, and is treated with Herceptin.
Ironically ErbB2 is expressed variably in a variety of normal tissues(ref: Press, M.F., C. Cordon-Cardo, and D.J. Slamon, Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene, 1990. 5(7): p. 953-62. ), and in developing and diseased myocardium (3 Refs : Zhao, Y.Y., et al., Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem, 1998. 273(17): p. 10261-9.
Fuchs, I.B., et al., Analysis of HER2 and HER4 in human myocardium to clarify the cardiotoxicity of trastuzumab (Herceptin). Breast Cancer Res Treat, 2003. 82(1): p. 23-8.
Uray, I.P., et al., Left ventricular unloading alters receptor tyrosine kinase expression in the failing human heart. J Heart Lung Transplant, 2002. 21(7): p. 771-82.) and is therefore a poor example of a tumour specific antigen.
Jellytussle
02:47, 31 May 2006 (UTC)
OK fixed that, it's untrue.
Her-2 is found in many cell types and tissues, but it is only overexpressed in some types of cancer, and that's the critical thing with Herceptin.
-- Cellpath 01:17, 3 June 2006 (UTC)
Apart from the intro there isn't much on cancer vaccines. Needs summary here ?
No mention of TLR9 agonists eg "Prostate Cancer: Genes, Environment, Immunity and the use of Immunotherapy: TLR9 Agonist in Immunotherapy" 2008 but I think this would be a whole new category here. Rod57 ( talk) 03:53, 20 January 2010 (UTC)
GD2 seems only mentioned in the Intro section. Presumably this should be moved to a new section further down the article ? Rod57 ( talk) 04:28, 20 January 2010 (UTC)
This section contains information on the immune effects of various mushroom, most not clearly related to clinical medicine, with no mention of clinical studies etc, particularly with respect to cancer treatment. One product is mentioned as being "commercially available in Australia" which means very little if one can buy it over the counter from a health food shop. Propose delete the entire section unless it can be seriously beefed up. Jellytussle ( talk) 15:34, 10 August 2011 (UTC)
has material should probably be here, especially the history section which appears to be completely absent here. 72.228.177.92 ( talk) 10:32, 12 January 2012 (UTC)
Under Advances it says "Another strategy is to deliver a lethal radioactive dose directly to the target cell, which has been utilized in the case of the Zevalin therapeutic. A third strategy is to deliver a lethal chemical dose to the target, as used in the Mylotarg therapeutic"
but since that doesn't affect the host immune system shouldn't we exclude these ? They seem to be
targeted therapys as mentioned above. -
Rod57 (
talk)
12:27, 11 April 2013 (UTC)
Hi Alexbrn, You removed some content on the cancer immunotherapy article regarding new information by the National Cancer Institute, National Institute of Health, and Science Magazine/Journal, with the stated reason that WP:MEDRS was violated. These sources are very reliable, and many more sources on the subject are available with a quick google search. You seem to be a valuable member of the wikipedia community, have edited many articles, and I believe I saw that you are a cancer survivor yourself. My family has been affected by cancer as well. I'm confused why you wouldn't want information regarding one of the most promising avenues of cancer immunotherapy treatment added to the cancer immunotherapy article. Thx Whodat2112 ( talk) 15:27, 10 May 2014 (UTC)
Alexbrn, you make a good point, but it's important to remember that these are two separate subjects you are referring to. For the study of CAR T Cell therapy on ALL patients, I was actually understating the results. The actual result was an 89 percent complete remission for the 27 patients that were studied (22 children and 5 adults), of which the majority of patients are still in complete remission. These results were published about 1 year ago and can be verified by many reliable secondary sources such as The American Society of Hematology and the American Society of Clinical Oncology:
http://www.hematology.org/Newsroom/Press-Releases/2013/1322.aspx
For the study on Personalized ACT starting with whole-exome sequencing to target TIL's, this is a very recent discovery that CAR T Cell Therapy can be used to target epithelial cancers. Besides the NCI, NIH, and Science Magazine Primary sources, I can offer secondary sources such as webmd, the wall street journal, and fiercebiotech:
wsj&url=http%3A%2F%2Fonline.wsj.com%2Farticle%2FSB10001424052702303701304579550101737391142.html%3Fmod%3DWSJ_LatestHeadlines
http://www.fiercebiotech.com/story/new-immunotherapy-uses-patients-cells-attack-tumors/2014-05-09
If you feel that either of these discoveries are not established enough to put in the Adoptive T Cell Therapy Section, I would be happy to put them in the "New and Future Immunotherapies Section". Please let me know how you would like me to proceed when you get a chance. Whodat2112 ( talk) 18:30, 10 May 2014 (UTC)
Alexbrn, I added the sentence you suggested "As of 2014, clinical trials for ACT are underway, and preliminary results are promising." and sourced the NIH and NCI references. I'm ok with this compromise to describe the state of ACT clinical trials, but I think we are still missing important info about the discovery that ACT which starts with whole-exome sequencing has the potential to work on epithelial cancers, which is a major breakthrough in our understanding of ACT's potential in cancer treatment beyond just blood based cancers. I'm open to your thoughts though. Whodat2112 ( talk) 21:07, 10 May 2014 (UTC)
The following antibodies mentioned in this article appear to work by mechanisms other than activation of the immune system:
Hence they do not appear relevant to this article but would be relevant for Monoclonal antibody therapy. Am I missing something? Boghog ( talk) 12:31, 26 June 2015 (UTC)
I have gone ahead and removed the above list of antibodies from this article. Boghog ( talk) 05:20, 30 June 2015 (UTC)
Immunotherapies are treatments that restore or enhance the immune system's ability to fight cancer.
Immunotherapy is treatment that uses certain parts of a person's immune system to fight diseases such as cancer. ... Immunotherapy includes treatments that work in different ways. Some boost the body's immune system in a very general way. Others help train the immune system to attack cancer cells specifically.
Immunotherapy, also called biologic therapy, is a type of cancer treatment designed to boost the body's natural defenses to fight the cancer. ... There are several types of immunotherapy, including monoclonal antibodies, non-specific immunotherapies, and cancer vaccines.
The Immune checkpoint blockade section could start new article. Could call it checkpoint inhibitor therapy ? Possibly also split out PD-1 inhibitor since there are other types of Immune checkpoint blockade - see Immune checkpoint. - Rod57 ( talk) 18:56, 22 June 2016 (UTC)
Lfstevens has been doing some great work on IT across several articles; this is something that really needed doing, so thanks for that!
This content however is UNDUE on a single mouse study
In 2015 a study on mice with an aggressive form of melanoma, simultaneously applied antibody therapy, activating the innate immune system and adoptive cell transfer, stimulating the adaptive immune system. A signaling molecule called IL-2 generated both types of immune responses. Building on earlier attempts to use the molecule, the research extended IL-2's duration in the bloodstream by fusing to to part of an antibody molecule. The study concluded that a weekly dose of IL-2 with antibodies could stop tumor growth. [1] [2] [3]
T cells were the most important component of the anti-tumor response induced by the antibody-IL-2 combination. They combination of IL-2-induced cells and cytokines with the antibody treatment allowed T cells to attack more effectively. Neutrophils that react strongly to foreign invaders entering the body through a cut or other injury were also important. Adoptively transferred T cells that targeted the tumor were more effective when delivered with an antibody and IL-2. In 80 to 90% of the mice, tumors disappeared completely. Tumor cells that were re-injected into the mice months after the original treatment were killed by the immune system, preventing new tumors from forming. More generally IL-2 bound to antibodies that did not target a protein on the tumor cell surface, still halted or slowed tumor growth. [1] [2] [3]
References
There is a lot of media hype around IT (per the sources here) and we need to go really, really lightly on that stuff, per WP:MEDREV which explicitly talks about this. Jytdog ( talk) 00:24, 10 April 2016 (UTC)
History includes "Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it." with no reference or explanation of how it relates to cancer immunotherapy. (Could someone improve it ?) -
Coley's toxins, in use (in humans) 1893 to 1963 (USA), to 1990 (Germany) seem as/more relevant. - Any objection to a brief mention of
Coley's toxins in the History section ? -
Rod57 (
talk)
13:00, 27 May 2016 (UTC)
And also
this review mentions it. -
Rod57 (
talk)
11:56, 2 July 2016 (UTC)
History says "In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011)." but it is not clear if any of these relate to 'cancer immunotherapy' (which is modification of the immune response, NOT the mere use of antibodies) - Rod57 ( talk) 21:48, 12 June 2016 (UTC)
... Looks like (from comments above) that some prior editors had a wider definition of Cancer immunotherapy but the excess content has not yet been purged. Any objections to eg that "In 1997 ..." sentence being removed ? - Rod57 ( talk) 21:57, 12 June 2016 (UTC)
Novel cancer antigens for personalized immunotherapies: latest evidence and clinical potential. Jan 2016 looks useful. - Rod57 ( talk) 12:05, 2 July 2016 (UTC)
It has been proposed that this cancer immunotherapy be merged with cancer immunology.
The following was added in these diffs; this is all sourced to primary sources by the subject being described - we need secondary sources saying this. As it stands this is WP:OR and WP:UNDUE:
Cancer immunogene therapy was introduced by Jerzy Trojan and colleagues in 1993, applying a subcutaneous injection of autologous cancer cells transfected with vector expressing antisense IGF-I RNA, [1]; [2] the clinical trial of glioblastoma was approved by NIH n˚ 1602, and FDA in 1994. The modified strategy using anti – gene (antisense / triple helix) anti IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial - n˚ 635 and 636; the clinical protocol was conducted by J. Trojan through the Collaborative NATO Science Program (USA, France, Poland n˚ LST 980517) and later in Colombia. [3] This cell-based immunotherapy has proven to be efficient, strengthening anti-tumor immune response (TCD8, TCD28) and apoptotic phenomena. Promising results were obtained in personalized treatments of glioblastoma, prostate, ovary, uterus, liver and colon cancer. [4]
References
-- Jytdog ( talk) 23:54, 2 January 2017 (UTC)
User:Mjenik you are adding content that is unsupported by its source, and that is promotional. A paper published on Y date about X, cannot itself be a source for X being first on Y date. That is WP:OR. The content is explicitly promotional as well, in violation of the WP:PROMO policy. Jytdog ( talk) 14:50, 17 October 2017 (UTC)
User:Jytdog I am adding the first paper who presents an anticancer CAR-T cell. http://www.pnas.org/content/86/24/10024.full.pdf You can look also at this patent. http://www.google.com/patents/US7741465 As I see I am not violating any policy as I am not doing promotion but I am recognizing the merit of the pioneers of the CAR. Whats would it be the way of claiming X was the first on Y date ? What more evidence should I bring ? I am showing a very very early journal publication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149517/. You will not find anyone from before. I assure you. I am also showing you here a patent from those dates. These team also developed the first ScFv on that moment. But this is another discussion.
Please allow the content to be there. They deserve the credit. — Preceding unsigned comment added by Mjenik ( talk • contribs) 16:48, 17 October 2017 (UTC)
References
{{
cite journal}}
: CS1 maint: PMC format (
link)
Dear @ Jytdog: , @ RexxS: and reviewers, thank you. Here are two quite valuable secondary sources. Carl June writes "The concept of introducing into a cytotoxic T-cell hybridoma the genetic material for an antibody recognizing a model antigen (a hapten, 2,4,6-trinitrophenyl) was described in 1989 by Gross, Waks, and Eshhar" and "The above basic science advances demonstrated that it was possible to redirect T-cell signaling to an antigen of choice and independent of MHC restrictions. In their seminal work, Gross et al. (9) concluded that ‘construction of chimeric T-cell receptors with anti-tumor specificity will enable testing of the feasibility of this approach in combating human tumors.’ " on. [1]
Steve Rosenberg writes "CARs were pioneered by Gross and colleagues in the late 1980s (45) and can be constructed by linking the variable regions of the antibody heavy and light chains to intracellular signaling chains such as CD3-zeta ..." on. [2] Mjenik ( talk) 12:47, 23 October 2017 (UTC)
Seeing the total absence of a history section in the article, I read the comment below, and inserted a brief history section that comes entirely from NIH PMC (freely available medical journal articles). Feel free to improve it, but deleting the entire history is absurd. Immunotherapy itself is not a new invention; the history goes back more than 4,000 years.<end of what I'm typing, someone else typed what is below.>
moved here as this is built from primary sources and editors are spatting over how to build content from primary sources which is never resolveable.
This needs to be done over based on independent (in other words, not written by the person who is claiming they were very important) secondary sources.
Immunotherapy for the treatment of cancer has been utilized throughout history, with the earliest report in 2600 BC, by Egyptian pharaoh Imhotep who had a poultice, followed by incision, to facilitate the development of infection in the desired location and cause regression of the tumour. In 13th century, St. Peregrine is reported to have experienced spontaneous regression of tumor, after the tumor became infected. [3] In the 18th and 19th centuries, deliberate infection of tumors were a standard treatment, where surgical wounds were left open to facilitate the development of infection. Throughout the time period, physicians reported successful treatment of cancer by exposing the tumor to infection including the report of French physician Dussosoy who covered an ulcerated breast carcinoma with gangrenous discharge soaked clothe, resulting in disappearance of tumor. [4] [5] [6] Observations of a relationship between infection and cancer regression date back to at least the 18th century. [7] [8] [9]
Modern Immunotherapy began in 1796 when Edward Jenner produced the first vaccine involving immunisation with cowpox to prevent smallpox. Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it.
Dr. William Coley, father of modern oncological immunotherapy, pioneered the treatment of cancer with immunotherapy based on bacterial vaccination with Coley's Toxins. [10] He developed a treatment based on provoking an immune response to bacteria. In 1968 a protein related to his work was identified and called tumor necrosis factor-alpha. [11]
Paul Ehrlich's research gave rise to the " magic bullet" concept; using antibodies to specifically target a disease. The production of pure monoclonal antibodies for therapeutic use became available in 1975 when Georges J. F. Köhler and Cesar Milstein produced hybridoma technology.
Immune cell therapy for cancer was introduced by Steven Rosenberg and colleagues. In the late 1980s, they reported a low tumor regression rate (2.6–3.3%) in 1205 patients with metastatic cancer who underwent different types of active specific immunotherapy. [12]
In 1987, cytotoxic T-lymphocyte antigen 4, or CTLA-4 was identified by Pierre Golstein and colleagues [13]. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice [14]. In 1999, biotech firm Medarex acquired rights to the antibody. In 2010, Bristol-Myers Squibb, who acquired Medarex in 2009, reported that patients with metastatic melanoma lived an average of 10 months on the antibody, versus 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial. [15]
In the early 1990s, a Tasuku Honjo and colleagues discovered a molecule expressed in dying T cells, which they called programmed death 1, or PD-1 [16] and which they recognized as another disabler of T cells. An antibody that targeted PD-1 was developed and by 2008 produced remission in multiple subjects across multiple cancer types. In 2013, clinicians reported that across 300 patients tumors shrunk by about half or more in 31% of those with melanoma, 29% with kidney cancer and 17% with lung cancer. [15]
In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011).
In 2003 cytokines such as interleukin were administered. [17] The adverse effects of intravenously administered cytokines [18] led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells [19] with appropriate stimulatory cytokines.
However, with both anti–CTLA-4 and anti–PD-1, some tumors continued to grow before vanishing months later. Some patients kept responding after the antibody had been discontinued. Some patients, developed side effects including inflammation of the colon or of the pituitary gland. [15]
The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer. [20] [21]
After success harvesting T cells from tumors, expanding them in the lab and reinfusing them into patients reduced tumors, in 2010, Steven Rosenberg announced the feasibility of chimeric antigen receptor (CAR) therapy, invented on 1989 by Gideon Gross and Zelig Eshhar [1][2]. This technique is a personalized treatment that involves genetically modifying each patient's T cells to target tumor cells. It produced complete remission in a majority of leukemia patients, although some later relapsed. [15]
By mid 2016 the FDA had approved one PD-L1 inhibitor ( atezolizumab) and two PD-1 inhibitors ( nivolumab and pembrolizumab).
References
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
{{
cite web}}
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help)
Waldmann
was invoked but never defined (see the
help page).-- Jytdog ( talk) 20:38, 26 October 2017 (UTC)
This is how the section looked like before going off but with the addition of a sentence to mention the invention of the CAR on late 80s. Of course this fact is supported by citations of respected secondary sources.
Immunotherapy for the treatment of cancer has been utilized throughout history, with the earliest report in 2600 BC, by Egyptian pharaoh Imhotep who had a poultice, followed by incision, to facilitate the development of infection in the desired location and cause regression of the tumour. In 13th century, St. Peregrine is reported to have experienced spontaneous regression of tumor, after the tumor became infected. [1] In the 18th and 19th centuries, deliberate infection of tumors were a standard treatment, where surgical wounds were left open to facilitate the development of infection. Throughout the time period, physicians reported successful treatment of cancer by exposing the tumor to infection including the report of French physician Dussosoy who covered an ulcerated breast carcinoma with gangrenous discharge soaked clothe, resulting in disappearance of tumor. [2] [3] [4] Observations of a relationship between infection and cancer regression date back to at least the 18th century. [5] [6] [7]
Modern Immunotherapy began in 1796 when Edward Jenner produced the first vaccine involving immunisation with cowpox to prevent smallpox. Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it.
Dr. William Coley, father of modern oncological immunotherapy, pioneered the treatment of cancer with immunotherapy based on bacterial vaccination with Coley's Toxins. [8] He developed a treatment based on provoking an immune response to bacteria. In 1968 a protein related to his work was identified and called tumor necrosis factor-alpha. [9]
Paul Ehrlich's research gave rise to the " magic bullet" concept; using antibodies to specifically target a disease. The production of pure monoclonal antibodies for therapeutic use became available in 1975 when Georges J. F. Köhler and Cesar Milstein produced hybridoma technology.
Immune cell therapy for cancer was introduced by Steven Rosenberg and colleagues. In the late 1980s, they reported a low tumor regression rate (2.6–3.3%) in 1205 patients with metastatic cancer who underwent different types of active specific immunotherapy. [10]
In 1987, cytotoxic T-lymphocyte antigen 4, or CTLA-4 was identified by Pierre Golstein and colleagues [11]. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice [12]. In 1999, biotech firm Medarex acquired rights to the antibody. In 2010, Bristol-Myers Squibb, who acquired Medarex in 2009, reported that patients with metastatic melanoma lived an average of 10 months on the antibody, versus 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial. [13]
In the early 1990s, a Tasuku Honjo and colleagues discovered a molecule expressed in dying T cells, which they called programmed death 1, or PD-1 [14] and which they recognized as another disabler of T cells. An antibody that targeted PD-1 was developed and by 2008 produced remission in multiple subjects across multiple cancer types. In 2013, clinicians reported that across 300 patients tumors shrunk by about half or more in 31% of those with melanoma, 29% with kidney cancer and 17% with lung cancer. [13]
In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011).
In 2003 cytokines such as interleukin were administered. [15] The adverse effects of intravenously administered cytokines [16] led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells [17] with appropriate stimulatory cytokines.
However, with both anti–CTLA-4 and anti–PD-1, some tumors continued to grow before vanishing months later. Some patients kept responding after the antibody had been discontinued. Some patients, developed side effects including inflammation of the colon or of the pituitary gland. [13]
The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer. [18] [19]
After success harvesting T cells from tumors, expanding them in the lab and reinfusing them into patients reduced tumors, in 2010, Steven Rosenberg announced the feasibility of chimeric antigen receptor (CAR) therapy, invented on 1989 by Gideon Gross and Zelig Eshhar [20]. [21] This technique is a personalized treatment that involves genetically modifying each patient's T cells to target tumor cells. It produced complete remission in a majority of leukemia patients, although some later relapsed. [13]
By mid 2016 the FDA had approved one PD-L1 inhibitor ( atezolizumab) and two PD-1 inhibitors ( nivolumab and pembrolizumab).
References
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
{{
cite web}}
: Unknown parameter |dead-url=
ignored (|url-status=
suggested) (
help)
Waldmann
was invoked but never defined (see the
help page).I rewrote the outdated anti-CD47 therapy section. I used primary sources and assume this was the reason the new author, Jytdog, didn't like it and deleted the whole paragraph leaving just one sentence. I wonder if it is not too little. I feel like at least the most important parts could have been left there and the sources just replaced from primary ones to reviews. Jan Kuzmik ( talk) 20:20, 1 March 2018 (UTC) — Preceding unsigned comment added by Jan Kuzmik ( talk • contribs) 20:18, 1 March 2018 (UTC)
Why isn't the BCG vaccine (Bacillus Calmette–Guérin) listed here? It is a live vaccine containing Mycobacterium bovis used to protect against tuberculosis, but it has also been (very successfully) used as immunotherapy treatment for bladder cancer since the 1970s. I'm not sure which category, if any, it would fit into in this article, otherwise I'd add it. 2602:304:1064:8429:99F8:11E3:B8CC:2619 ( talk) 15:02, 18 May 2020 (UTC)
I'm not entirely sure the categorization of active or passive is really necessary or useful. I've found multiple different definitions for active vs passive, and different classifications of what each agent is considered (see discussion here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350348/). I've made edits based on what I perceived as the distinguishing features of active vs passive, but would be interested to see if perhaps we should skip this section entirely and just focus on the different sub-types of immunotherapy. Quokkarobocop ( talk) — Preceding undated comment added 04:17, 1 December 2020 (UTC)
Lifestyle is the biggest factor in determining the state of the immune system. Yet it is not even mentioned. This is pathetic... 192.0.202.25 ( talk) 05:32, 24 October 2023 (UTC)
Prior content in this article duplicated one or more previously published sources. The material was copied from:
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For legal reasons, we cannot accept copyrighted text or images borrowed from other web sites or published material; such additions will be deleted. Contributors may use copyrighted publications as a source of information, and, if allowed under fair use, may copy sentences and phrases, provided they are included in quotation marks and referenced properly. The material may also be rewritten, provided it does not infringe on the copyright of the original or plagiarize from that source. Therefore, such paraphrased portions must provide their source. Please see our guideline on non-free text for how to properly implement limited quotations of copyrighted text. Wikipedia takes copyright violations very seriously, and persistent violators will be blocked from editing. While we appreciate contributions, we must require all contributors to understand and comply with these policies. Thank you. begocc questions? 12:50, 12 April 2024 (UTC)
Came here via rediect of immune checkpoint inhibitors (ICIs), in order to update. Found it mentioned right at the beginning in the introduction, but then only buried under research ! Why on earth ? They are no longer research only. There are even numerous less important single sentence sections crammed in above. The initial outline does not fit with what follows. Also, "Combination immunotherapy" is nothing but immune checkpoint inhibitors combination, belongs there. Animal experiments, even if they are worth mentioning should be under the respective child- pages. Wuerzele ( talk) 17:35, 21 April 2024 (UTC)
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Above undated message substituted from Template:Dashboard.wikiedu.org assignment by PrimeBOT ( talk) 16:39, 16 January 2022 (UTC)
Cancer Immunotherapy is the use of the immune system to reject cancer. The main premise is stimulating the patient's immune system to attack the malignant tumor cells that are responsible for the disease.
This is an incorrect generalisation, and as such should not be part of the opening paragraph, if TK inhibitors and radioimmunotherapy are classed as part of cancer immunotherapy, rather than as targeted therapy. Whilst immune stimulation is a strategy, this is emphatically not the technique used by most of the commercial monoclonals used today eg the tyrosine kinase inhibitors such as Herceptin, Cetuximab, which interfere with the ErbB family. Nor is it the mode of action of the radioconjugates such as Zevalin, or Bexxar. Jellytussle 20:12, 11 May 2006 (UTC)
It is generally accecpted that cancer immunotherapy refers to the use of monoclonal antibodies in the treatment of cancer, so I have removed references to IL-2, artificial T cell receptors, Imiquimod and vaccines. They would be more approiately placed in an article on immune modification or immune modifiers.
The problem is that this makes the opening paragraph even more irrelevant. I think it is instructive to look at a respectable and authoritative source for a good summary of definitions. This is taken from the Cancer Research UK website:
"Immunotherapy
* It can stop the cancer from growing by stopping other essential 'growth factors' from sticking to it. * It can 'tag' the cancer for destruction by the immune system. * If cancer drugs or radioactive particles are attached to the antibody, it can deliver them directly to the cancer cell without harming the rest of your body. * An enzyme (a type of protein that can promote chemical reactions) can be attached to an antibody, and then given to a patient along with a chemical that can be turned into a powerful drug by the enzyme. This directs the drug to the cancer, and minimise side effects. This process is known as Antibody-directed Enzyme/Pro-drug Therapy (ADEPT).
Jellytussle 23:47, 30 May 2006 (UTC)
Yes, Immunotherapy is a very ambigious name, as many immunological-based techniques are employed in cancer treatment. Monoclonal antibody therapy is a very distinct and high profile treatment, so it requires its own article. Maybe we should rename this article with something more specific and use "Immunotherapy" as an all encompasing aricle on immunological-based treatments in cancer. -- Cellpath 01:17, 3 June 2006 (UTC)
Other kinds of tumor cells display cell surface receptors that are rare or absent on the surfaces of healthy cells, and which are responsible for activating cellular signaling pathways that cause the unregulated growth and division of the tumor cell. Examples include ErbB2, a constitutively active cell surface receptor that is produced at abnormally high levels on the surface of appromimately 30% of breast cancer tumor cells. Such breast cancer is known a Her-2 positive breast cancer, and is treated with Herceptin.
Ironically ErbB2 is expressed variably in a variety of normal tissues(ref: Press, M.F., C. Cordon-Cardo, and D.J. Slamon, Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene, 1990. 5(7): p. 953-62. ), and in developing and diseased myocardium (3 Refs : Zhao, Y.Y., et al., Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem, 1998. 273(17): p. 10261-9.
Fuchs, I.B., et al., Analysis of HER2 and HER4 in human myocardium to clarify the cardiotoxicity of trastuzumab (Herceptin). Breast Cancer Res Treat, 2003. 82(1): p. 23-8.
Uray, I.P., et al., Left ventricular unloading alters receptor tyrosine kinase expression in the failing human heart. J Heart Lung Transplant, 2002. 21(7): p. 771-82.) and is therefore a poor example of a tumour specific antigen.
Jellytussle
02:47, 31 May 2006 (UTC)
OK fixed that, it's untrue.
Her-2 is found in many cell types and tissues, but it is only overexpressed in some types of cancer, and that's the critical thing with Herceptin.
-- Cellpath 01:17, 3 June 2006 (UTC)
Apart from the intro there isn't much on cancer vaccines. Needs summary here ?
No mention of TLR9 agonists eg "Prostate Cancer: Genes, Environment, Immunity and the use of Immunotherapy: TLR9 Agonist in Immunotherapy" 2008 but I think this would be a whole new category here. Rod57 ( talk) 03:53, 20 January 2010 (UTC)
GD2 seems only mentioned in the Intro section. Presumably this should be moved to a new section further down the article ? Rod57 ( talk) 04:28, 20 January 2010 (UTC)
This section contains information on the immune effects of various mushroom, most not clearly related to clinical medicine, with no mention of clinical studies etc, particularly with respect to cancer treatment. One product is mentioned as being "commercially available in Australia" which means very little if one can buy it over the counter from a health food shop. Propose delete the entire section unless it can be seriously beefed up. Jellytussle ( talk) 15:34, 10 August 2011 (UTC)
has material should probably be here, especially the history section which appears to be completely absent here. 72.228.177.92 ( talk) 10:32, 12 January 2012 (UTC)
Under Advances it says "Another strategy is to deliver a lethal radioactive dose directly to the target cell, which has been utilized in the case of the Zevalin therapeutic. A third strategy is to deliver a lethal chemical dose to the target, as used in the Mylotarg therapeutic"
but since that doesn't affect the host immune system shouldn't we exclude these ? They seem to be
targeted therapys as mentioned above. -
Rod57 (
talk)
12:27, 11 April 2013 (UTC)
Hi Alexbrn, You removed some content on the cancer immunotherapy article regarding new information by the National Cancer Institute, National Institute of Health, and Science Magazine/Journal, with the stated reason that WP:MEDRS was violated. These sources are very reliable, and many more sources on the subject are available with a quick google search. You seem to be a valuable member of the wikipedia community, have edited many articles, and I believe I saw that you are a cancer survivor yourself. My family has been affected by cancer as well. I'm confused why you wouldn't want information regarding one of the most promising avenues of cancer immunotherapy treatment added to the cancer immunotherapy article. Thx Whodat2112 ( talk) 15:27, 10 May 2014 (UTC)
Alexbrn, you make a good point, but it's important to remember that these are two separate subjects you are referring to. For the study of CAR T Cell therapy on ALL patients, I was actually understating the results. The actual result was an 89 percent complete remission for the 27 patients that were studied (22 children and 5 adults), of which the majority of patients are still in complete remission. These results were published about 1 year ago and can be verified by many reliable secondary sources such as The American Society of Hematology and the American Society of Clinical Oncology:
http://www.hematology.org/Newsroom/Press-Releases/2013/1322.aspx
For the study on Personalized ACT starting with whole-exome sequencing to target TIL's, this is a very recent discovery that CAR T Cell Therapy can be used to target epithelial cancers. Besides the NCI, NIH, and Science Magazine Primary sources, I can offer secondary sources such as webmd, the wall street journal, and fiercebiotech:
wsj&url=http%3A%2F%2Fonline.wsj.com%2Farticle%2FSB10001424052702303701304579550101737391142.html%3Fmod%3DWSJ_LatestHeadlines
http://www.fiercebiotech.com/story/new-immunotherapy-uses-patients-cells-attack-tumors/2014-05-09
If you feel that either of these discoveries are not established enough to put in the Adoptive T Cell Therapy Section, I would be happy to put them in the "New and Future Immunotherapies Section". Please let me know how you would like me to proceed when you get a chance. Whodat2112 ( talk) 18:30, 10 May 2014 (UTC)
Alexbrn, I added the sentence you suggested "As of 2014, clinical trials for ACT are underway, and preliminary results are promising." and sourced the NIH and NCI references. I'm ok with this compromise to describe the state of ACT clinical trials, but I think we are still missing important info about the discovery that ACT which starts with whole-exome sequencing has the potential to work on epithelial cancers, which is a major breakthrough in our understanding of ACT's potential in cancer treatment beyond just blood based cancers. I'm open to your thoughts though. Whodat2112 ( talk) 21:07, 10 May 2014 (UTC)
The following antibodies mentioned in this article appear to work by mechanisms other than activation of the immune system:
Hence they do not appear relevant to this article but would be relevant for Monoclonal antibody therapy. Am I missing something? Boghog ( talk) 12:31, 26 June 2015 (UTC)
I have gone ahead and removed the above list of antibodies from this article. Boghog ( talk) 05:20, 30 June 2015 (UTC)
Immunotherapies are treatments that restore or enhance the immune system's ability to fight cancer.
Immunotherapy is treatment that uses certain parts of a person's immune system to fight diseases such as cancer. ... Immunotherapy includes treatments that work in different ways. Some boost the body's immune system in a very general way. Others help train the immune system to attack cancer cells specifically.
Immunotherapy, also called biologic therapy, is a type of cancer treatment designed to boost the body's natural defenses to fight the cancer. ... There are several types of immunotherapy, including monoclonal antibodies, non-specific immunotherapies, and cancer vaccines.
The Immune checkpoint blockade section could start new article. Could call it checkpoint inhibitor therapy ? Possibly also split out PD-1 inhibitor since there are other types of Immune checkpoint blockade - see Immune checkpoint. - Rod57 ( talk) 18:56, 22 June 2016 (UTC)
Lfstevens has been doing some great work on IT across several articles; this is something that really needed doing, so thanks for that!
This content however is UNDUE on a single mouse study
In 2015 a study on mice with an aggressive form of melanoma, simultaneously applied antibody therapy, activating the innate immune system and adoptive cell transfer, stimulating the adaptive immune system. A signaling molecule called IL-2 generated both types of immune responses. Building on earlier attempts to use the molecule, the research extended IL-2's duration in the bloodstream by fusing to to part of an antibody molecule. The study concluded that a weekly dose of IL-2 with antibodies could stop tumor growth. [1] [2] [3]
T cells were the most important component of the anti-tumor response induced by the antibody-IL-2 combination. They combination of IL-2-induced cells and cytokines with the antibody treatment allowed T cells to attack more effectively. Neutrophils that react strongly to foreign invaders entering the body through a cut or other injury were also important. Adoptively transferred T cells that targeted the tumor were more effective when delivered with an antibody and IL-2. In 80 to 90% of the mice, tumors disappeared completely. Tumor cells that were re-injected into the mice months after the original treatment were killed by the immune system, preventing new tumors from forming. More generally IL-2 bound to antibodies that did not target a protein on the tumor cell surface, still halted or slowed tumor growth. [1] [2] [3]
References
There is a lot of media hype around IT (per the sources here) and we need to go really, really lightly on that stuff, per WP:MEDREV which explicitly talks about this. Jytdog ( talk) 00:24, 10 April 2016 (UTC)
History includes "Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it." with no reference or explanation of how it relates to cancer immunotherapy. (Could someone improve it ?) -
Coley's toxins, in use (in humans) 1893 to 1963 (USA), to 1990 (Germany) seem as/more relevant. - Any objection to a brief mention of
Coley's toxins in the History section ? -
Rod57 (
talk)
13:00, 27 May 2016 (UTC)
And also
this review mentions it. -
Rod57 (
talk)
11:56, 2 July 2016 (UTC)
History says "In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011)." but it is not clear if any of these relate to 'cancer immunotherapy' (which is modification of the immune response, NOT the mere use of antibodies) - Rod57 ( talk) 21:48, 12 June 2016 (UTC)
... Looks like (from comments above) that some prior editors had a wider definition of Cancer immunotherapy but the excess content has not yet been purged. Any objections to eg that "In 1997 ..." sentence being removed ? - Rod57 ( talk) 21:57, 12 June 2016 (UTC)
Novel cancer antigens for personalized immunotherapies: latest evidence and clinical potential. Jan 2016 looks useful. - Rod57 ( talk) 12:05, 2 July 2016 (UTC)
It has been proposed that this cancer immunotherapy be merged with cancer immunology.
The following was added in these diffs; this is all sourced to primary sources by the subject being described - we need secondary sources saying this. As it stands this is WP:OR and WP:UNDUE:
Cancer immunogene therapy was introduced by Jerzy Trojan and colleagues in 1993, applying a subcutaneous injection of autologous cancer cells transfected with vector expressing antisense IGF-I RNA, [1]; [2] the clinical trial of glioblastoma was approved by NIH n˚ 1602, and FDA in 1994. The modified strategy using anti – gene (antisense / triple helix) anti IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial - n˚ 635 and 636; the clinical protocol was conducted by J. Trojan through the Collaborative NATO Science Program (USA, France, Poland n˚ LST 980517) and later in Colombia. [3] This cell-based immunotherapy has proven to be efficient, strengthening anti-tumor immune response (TCD8, TCD28) and apoptotic phenomena. Promising results were obtained in personalized treatments of glioblastoma, prostate, ovary, uterus, liver and colon cancer. [4]
References
-- Jytdog ( talk) 23:54, 2 January 2017 (UTC)
User:Mjenik you are adding content that is unsupported by its source, and that is promotional. A paper published on Y date about X, cannot itself be a source for X being first on Y date. That is WP:OR. The content is explicitly promotional as well, in violation of the WP:PROMO policy. Jytdog ( talk) 14:50, 17 October 2017 (UTC)
User:Jytdog I am adding the first paper who presents an anticancer CAR-T cell. http://www.pnas.org/content/86/24/10024.full.pdf You can look also at this patent. http://www.google.com/patents/US7741465 As I see I am not violating any policy as I am not doing promotion but I am recognizing the merit of the pioneers of the CAR. Whats would it be the way of claiming X was the first on Y date ? What more evidence should I bring ? I am showing a very very early journal publication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149517/. You will not find anyone from before. I assure you. I am also showing you here a patent from those dates. These team also developed the first ScFv on that moment. But this is another discussion.
Please allow the content to be there. They deserve the credit. — Preceding unsigned comment added by Mjenik ( talk • contribs) 16:48, 17 October 2017 (UTC)
References
{{
cite journal}}
: CS1 maint: PMC format (
link)
Dear @ Jytdog: , @ RexxS: and reviewers, thank you. Here are two quite valuable secondary sources. Carl June writes "The concept of introducing into a cytotoxic T-cell hybridoma the genetic material for an antibody recognizing a model antigen (a hapten, 2,4,6-trinitrophenyl) was described in 1989 by Gross, Waks, and Eshhar" and "The above basic science advances demonstrated that it was possible to redirect T-cell signaling to an antigen of choice and independent of MHC restrictions. In their seminal work, Gross et al. (9) concluded that ‘construction of chimeric T-cell receptors with anti-tumor specificity will enable testing of the feasibility of this approach in combating human tumors.’ " on. [1]
Steve Rosenberg writes "CARs were pioneered by Gross and colleagues in the late 1980s (45) and can be constructed by linking the variable regions of the antibody heavy and light chains to intracellular signaling chains such as CD3-zeta ..." on. [2] Mjenik ( talk) 12:47, 23 October 2017 (UTC)
Seeing the total absence of a history section in the article, I read the comment below, and inserted a brief history section that comes entirely from NIH PMC (freely available medical journal articles). Feel free to improve it, but deleting the entire history is absurd. Immunotherapy itself is not a new invention; the history goes back more than 4,000 years.<end of what I'm typing, someone else typed what is below.>
moved here as this is built from primary sources and editors are spatting over how to build content from primary sources which is never resolveable.
This needs to be done over based on independent (in other words, not written by the person who is claiming they were very important) secondary sources.
Immunotherapy for the treatment of cancer has been utilized throughout history, with the earliest report in 2600 BC, by Egyptian pharaoh Imhotep who had a poultice, followed by incision, to facilitate the development of infection in the desired location and cause regression of the tumour. In 13th century, St. Peregrine is reported to have experienced spontaneous regression of tumor, after the tumor became infected. [3] In the 18th and 19th centuries, deliberate infection of tumors were a standard treatment, where surgical wounds were left open to facilitate the development of infection. Throughout the time period, physicians reported successful treatment of cancer by exposing the tumor to infection including the report of French physician Dussosoy who covered an ulcerated breast carcinoma with gangrenous discharge soaked clothe, resulting in disappearance of tumor. [4] [5] [6] Observations of a relationship between infection and cancer regression date back to at least the 18th century. [7] [8] [9]
Modern Immunotherapy began in 1796 when Edward Jenner produced the first vaccine involving immunisation with cowpox to prevent smallpox. Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it.
Dr. William Coley, father of modern oncological immunotherapy, pioneered the treatment of cancer with immunotherapy based on bacterial vaccination with Coley's Toxins. [10] He developed a treatment based on provoking an immune response to bacteria. In 1968 a protein related to his work was identified and called tumor necrosis factor-alpha. [11]
Paul Ehrlich's research gave rise to the " magic bullet" concept; using antibodies to specifically target a disease. The production of pure monoclonal antibodies for therapeutic use became available in 1975 when Georges J. F. Köhler and Cesar Milstein produced hybridoma technology.
Immune cell therapy for cancer was introduced by Steven Rosenberg and colleagues. In the late 1980s, they reported a low tumor regression rate (2.6–3.3%) in 1205 patients with metastatic cancer who underwent different types of active specific immunotherapy. [12]
In 1987, cytotoxic T-lymphocyte antigen 4, or CTLA-4 was identified by Pierre Golstein and colleagues [13]. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice [14]. In 1999, biotech firm Medarex acquired rights to the antibody. In 2010, Bristol-Myers Squibb, who acquired Medarex in 2009, reported that patients with metastatic melanoma lived an average of 10 months on the antibody, versus 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial. [15]
In the early 1990s, a Tasuku Honjo and colleagues discovered a molecule expressed in dying T cells, which they called programmed death 1, or PD-1 [16] and which they recognized as another disabler of T cells. An antibody that targeted PD-1 was developed and by 2008 produced remission in multiple subjects across multiple cancer types. In 2013, clinicians reported that across 300 patients tumors shrunk by about half or more in 31% of those with melanoma, 29% with kidney cancer and 17% with lung cancer. [15]
In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011).
In 2003 cytokines such as interleukin were administered. [17] The adverse effects of intravenously administered cytokines [18] led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells [19] with appropriate stimulatory cytokines.
However, with both anti–CTLA-4 and anti–PD-1, some tumors continued to grow before vanishing months later. Some patients kept responding after the antibody had been discontinued. Some patients, developed side effects including inflammation of the colon or of the pituitary gland. [15]
The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer. [20] [21]
After success harvesting T cells from tumors, expanding them in the lab and reinfusing them into patients reduced tumors, in 2010, Steven Rosenberg announced the feasibility of chimeric antigen receptor (CAR) therapy, invented on 1989 by Gideon Gross and Zelig Eshhar [1][2]. This technique is a personalized treatment that involves genetically modifying each patient's T cells to target tumor cells. It produced complete remission in a majority of leukemia patients, although some later relapsed. [15]
By mid 2016 the FDA had approved one PD-L1 inhibitor ( atezolizumab) and two PD-1 inhibitors ( nivolumab and pembrolizumab).
References
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
{{
cite web}}
: Unknown parameter |dead-url=
ignored (|url-status=
suggested) (
help)
Waldmann
was invoked but never defined (see the
help page).-- Jytdog ( talk) 20:38, 26 October 2017 (UTC)
This is how the section looked like before going off but with the addition of a sentence to mention the invention of the CAR on late 80s. Of course this fact is supported by citations of respected secondary sources.
Immunotherapy for the treatment of cancer has been utilized throughout history, with the earliest report in 2600 BC, by Egyptian pharaoh Imhotep who had a poultice, followed by incision, to facilitate the development of infection in the desired location and cause regression of the tumour. In 13th century, St. Peregrine is reported to have experienced spontaneous regression of tumor, after the tumor became infected. [1] In the 18th and 19th centuries, deliberate infection of tumors were a standard treatment, where surgical wounds were left open to facilitate the development of infection. Throughout the time period, physicians reported successful treatment of cancer by exposing the tumor to infection including the report of French physician Dussosoy who covered an ulcerated breast carcinoma with gangrenous discharge soaked clothe, resulting in disappearance of tumor. [2] [3] [4] Observations of a relationship between infection and cancer regression date back to at least the 18th century. [5] [6] [7]
Modern Immunotherapy began in 1796 when Edward Jenner produced the first vaccine involving immunisation with cowpox to prevent smallpox. Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it.
Dr. William Coley, father of modern oncological immunotherapy, pioneered the treatment of cancer with immunotherapy based on bacterial vaccination with Coley's Toxins. [8] He developed a treatment based on provoking an immune response to bacteria. In 1968 a protein related to his work was identified and called tumor necrosis factor-alpha. [9]
Paul Ehrlich's research gave rise to the " magic bullet" concept; using antibodies to specifically target a disease. The production of pure monoclonal antibodies for therapeutic use became available in 1975 when Georges J. F. Köhler and Cesar Milstein produced hybridoma technology.
Immune cell therapy for cancer was introduced by Steven Rosenberg and colleagues. In the late 1980s, they reported a low tumor regression rate (2.6–3.3%) in 1205 patients with metastatic cancer who underwent different types of active specific immunotherapy. [10]
In 1987, cytotoxic T-lymphocyte antigen 4, or CTLA-4 was identified by Pierre Golstein and colleagues [11]. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice [12]. In 1999, biotech firm Medarex acquired rights to the antibody. In 2010, Bristol-Myers Squibb, who acquired Medarex in 2009, reported that patients with metastatic melanoma lived an average of 10 months on the antibody, versus 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial. [13]
In the early 1990s, a Tasuku Honjo and colleagues discovered a molecule expressed in dying T cells, which they called programmed death 1, or PD-1 [14] and which they recognized as another disabler of T cells. An antibody that targeted PD-1 was developed and by 2008 produced remission in multiple subjects across multiple cancer types. In 2013, clinicians reported that across 300 patients tumors shrunk by about half or more in 31% of those with melanoma, 29% with kidney cancer and 17% with lung cancer. [13]
In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011).
In 2003 cytokines such as interleukin were administered. [15] The adverse effects of intravenously administered cytokines [16] led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells [17] with appropriate stimulatory cytokines.
However, with both anti–CTLA-4 and anti–PD-1, some tumors continued to grow before vanishing months later. Some patients kept responding after the antibody had been discontinued. Some patients, developed side effects including inflammation of the colon or of the pituitary gland. [13]
The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer. [18] [19]
After success harvesting T cells from tumors, expanding them in the lab and reinfusing them into patients reduced tumors, in 2010, Steven Rosenberg announced the feasibility of chimeric antigen receptor (CAR) therapy, invented on 1989 by Gideon Gross and Zelig Eshhar [20]. [21] This technique is a personalized treatment that involves genetically modifying each patient's T cells to target tumor cells. It produced complete remission in a majority of leukemia patients, although some later relapsed. [13]
By mid 2016 the FDA had approved one PD-L1 inhibitor ( atezolizumab) and two PD-1 inhibitors ( nivolumab and pembrolizumab).
References
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
{{
cite web}}
: Unknown parameter |dead-url=
ignored (|url-status=
suggested) (
help)
Waldmann
was invoked but never defined (see the
help page).I rewrote the outdated anti-CD47 therapy section. I used primary sources and assume this was the reason the new author, Jytdog, didn't like it and deleted the whole paragraph leaving just one sentence. I wonder if it is not too little. I feel like at least the most important parts could have been left there and the sources just replaced from primary ones to reviews. Jan Kuzmik ( talk) 20:20, 1 March 2018 (UTC) — Preceding unsigned comment added by Jan Kuzmik ( talk • contribs) 20:18, 1 March 2018 (UTC)
Why isn't the BCG vaccine (Bacillus Calmette–Guérin) listed here? It is a live vaccine containing Mycobacterium bovis used to protect against tuberculosis, but it has also been (very successfully) used as immunotherapy treatment for bladder cancer since the 1970s. I'm not sure which category, if any, it would fit into in this article, otherwise I'd add it. 2602:304:1064:8429:99F8:11E3:B8CC:2619 ( talk) 15:02, 18 May 2020 (UTC)
I'm not entirely sure the categorization of active or passive is really necessary or useful. I've found multiple different definitions for active vs passive, and different classifications of what each agent is considered (see discussion here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350348/). I've made edits based on what I perceived as the distinguishing features of active vs passive, but would be interested to see if perhaps we should skip this section entirely and just focus on the different sub-types of immunotherapy. Quokkarobocop ( talk) — Preceding undated comment added 04:17, 1 December 2020 (UTC)
Lifestyle is the biggest factor in determining the state of the immune system. Yet it is not even mentioned. This is pathetic... 192.0.202.25 ( talk) 05:32, 24 October 2023 (UTC)
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Came here via rediect of immune checkpoint inhibitors (ICIs), in order to update. Found it mentioned right at the beginning in the introduction, but then only buried under research ! Why on earth ? They are no longer research only. There are even numerous less important single sentence sections crammed in above. The initial outline does not fit with what follows. Also, "Combination immunotherapy" is nothing but immune checkpoint inhibitors combination, belongs there. Animal experiments, even if they are worth mentioning should be under the respective child- pages. Wuerzele ( talk) 17:35, 21 April 2024 (UTC)