![]() | This article needs to be updated.(October 2021) |
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Mouse |
Target | αβ T Cell Receptor |
Clinical data | |
Routes of administration | Intravenous |
Legal status | |
Legal status |
|
Identifiers | |
CAS Number | |
ChemSpider |
|
UNII | |
(verify) |
TOL101, is a murine- monoclonal antibody specific for the human αβ T cell receptor. In 2010 it was an Investigational New Drug under development by Tolera Therapeutics, Inc.
TOL101 is a clinical stage investigational drug. The safety and efficacy of TOL101 is currently the focus of a phase 2 clinical trial in renal transplant patients.[ when?] [1]
TOL101 was granted "orphan drug" status [2] by the U.S. Food and Drug Administration for the treatment of recent onset immune-mediated Type 1 diabetes and for prophylaxis of acute rejection of solid organ transplantation.[ when?]
There are numerous agents currently under investigation that are capable of modulating T cells. Currently used agents include anti-thymocyte globulin(ATG) and alemtuzumab, which not only affect T cells, but are also capable of modulating many other aspects of the immune system, often resulting in long-term broad spectrum immune suppression. [1] [2] Antibodies specific for CD3 such as teplizumab and otelixizumab [3] show increased specificity for T cells compared to ATG and alemtuzumab, but are still associated with infection and cytokine release syndrome. Targeting the αβ T cells with TOL101 may reduce these issues through two mechanisms. First, infections are expected[ by whom?] to be reduced through the preservation of γδ T cells, [4] which have been shown to play an important role in controlling viruses such as cytomegalovirus (CMV), [5] often observed in antibody treated patients. Second, reductions in cytokine release are expected[ by whom?] when targeting the αβ TCR because, unlike CD3 proteins, the αβ TCR contains none of the immunoreceptor tyrosine-based activation motifs (ITAMS) required for T cell activation.[ citation needed]
TOL101 has been shown in in vitro models to specifically modulate αβ T cells. Incubation of peripheral blood monocytes (PBMC) with TOL101 triggers rapid down modulation of the T cell receptor. [6][ verification needed] Importantly, this occurs without T cell proliferation or cytokine induction. Examination of the ability of TOL101 to modulate T cells in a humanized mouse model not only confirmed these in vitro results but also suggested that the T cell modulating capability of the drug occurred in a non-depletional fashion. [7]
Targeting αβ T cells with antibodies has been tested in numerous experimental models of disease. The data suggests that in models of multiple sclerosis ( Experimental autoimmune encephalomyelitis [8]) and type 1 diabetes (Non-obese diabetic mice, [9]) anti-αβ TCR antibody therapy can ameliorate disease symptoms and progression.[ verification needed] The precise mechanism through which this occurs remains to be defined, however, it is likely to involve the induction of operational tolerance.[ citation needed]
TOL101 is a murine IgM antibody.
{{
cite journal}}
: CS1 maint: multiple names: authors list (
link)
{{
cite journal}}
: CS1 maint: multiple names: authors list (
link)
![]() | This article needs to be updated.(October 2021) |
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Mouse |
Target | αβ T Cell Receptor |
Clinical data | |
Routes of administration | Intravenous |
Legal status | |
Legal status |
|
Identifiers | |
CAS Number | |
ChemSpider |
|
UNII | |
(verify) |
TOL101, is a murine- monoclonal antibody specific for the human αβ T cell receptor. In 2010 it was an Investigational New Drug under development by Tolera Therapeutics, Inc.
TOL101 is a clinical stage investigational drug. The safety and efficacy of TOL101 is currently the focus of a phase 2 clinical trial in renal transplant patients.[ when?] [1]
TOL101 was granted "orphan drug" status [2] by the U.S. Food and Drug Administration for the treatment of recent onset immune-mediated Type 1 diabetes and for prophylaxis of acute rejection of solid organ transplantation.[ when?]
There are numerous agents currently under investigation that are capable of modulating T cells. Currently used agents include anti-thymocyte globulin(ATG) and alemtuzumab, which not only affect T cells, but are also capable of modulating many other aspects of the immune system, often resulting in long-term broad spectrum immune suppression. [1] [2] Antibodies specific for CD3 such as teplizumab and otelixizumab [3] show increased specificity for T cells compared to ATG and alemtuzumab, but are still associated with infection and cytokine release syndrome. Targeting the αβ T cells with TOL101 may reduce these issues through two mechanisms. First, infections are expected[ by whom?] to be reduced through the preservation of γδ T cells, [4] which have been shown to play an important role in controlling viruses such as cytomegalovirus (CMV), [5] often observed in antibody treated patients. Second, reductions in cytokine release are expected[ by whom?] when targeting the αβ TCR because, unlike CD3 proteins, the αβ TCR contains none of the immunoreceptor tyrosine-based activation motifs (ITAMS) required for T cell activation.[ citation needed]
TOL101 has been shown in in vitro models to specifically modulate αβ T cells. Incubation of peripheral blood monocytes (PBMC) with TOL101 triggers rapid down modulation of the T cell receptor. [6][ verification needed] Importantly, this occurs without T cell proliferation or cytokine induction. Examination of the ability of TOL101 to modulate T cells in a humanized mouse model not only confirmed these in vitro results but also suggested that the T cell modulating capability of the drug occurred in a non-depletional fashion. [7]
Targeting αβ T cells with antibodies has been tested in numerous experimental models of disease. The data suggests that in models of multiple sclerosis ( Experimental autoimmune encephalomyelitis [8]) and type 1 diabetes (Non-obese diabetic mice, [9]) anti-αβ TCR antibody therapy can ameliorate disease symptoms and progression.[ verification needed] The precise mechanism through which this occurs remains to be defined, however, it is likely to involve the induction of operational tolerance.[ citation needed]
TOL101 is a murine IgM antibody.
{{
cite journal}}
: CS1 maint: multiple names: authors list (
link)
{{
cite journal}}
: CS1 maint: multiple names: authors list (
link)