TOL101
Monoclonal antibody | |
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Type | Whole antibody |
Source | Mouse |
Target | |
Clinical data | |
Routes of administration | Intravenous |
Legal status | |
Legal status |
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TOL101, is a murine-monoclonal antibody specific for the human
Clinical progress
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.[1]
Orphan drug status
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.
Rationale for development
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
Mechanism of action
TOL101 modulates α β T cells
TOL101 has been shown in in vitro models to specifically modulate
α β T cells antibodies in experimental disease models
Targeting
Chemistry
TOL101 is a murine IgM antibody.
References
- ^ Brennan, DC, Daller JA, Lake KD, Cibrik D, Del Castillo D (2006). "Rabbit antithymocyte globulin versus basiliximab in renal transplantation". N Engl J Med. 355 (19): 1967–77. doi:10.1056/NEJMoa060068. PMID 17093248.
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: CS1 maint: multiple names: authors list (link) - ^ Mohty M (2007). "Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond". Leukemia. 21 (7): 1387–94. doi:10.1038/sj.leu.2404683. PMID 17410187.
- ^ Chatenoud L (2010). "Immune therapy for type 1 diabetes mellitus-what is unique about anti-CD3 antibodies?". Nat Rev Endocrinol. 6 (3): 149–157. doi:10.1038/nrendo.2009.275. PMID 20173776.
- ^ Beetz S, Wesch D, Marischen L, Welte S, Oberg HH, Kabelitz D (2008). "Innate immune functions of human gammadelta T cells". Immunobiology. 213 (3–4): 173–82. doi:10.1016/j.imbio.2007.10.006. PMID 18406365.
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: CS1 maint: multiple names: authors list (link) - ^ Lafarge X, Merville P, Cazin MC, Berge F, Potaux L, Moreau JF, Dechanet-Merville J (2001). "Cytomegalovirus infection in transplant recipients resolves when circulating gammadelta T lymphocytes expand, suggesting a protective antiviral role". J Infect Dis. 184 (5): 533–41. doi:10.1086/322843. PMID 11494158.
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: CS1 maint: multiple names: authors list (link) - ^ Getts DR, Brown S, Siemionow M, Miller, SD. "TOL101; a new aid to prevent allograft rejection". American Journal of Transplantation. 9 (Suppl 2): 991–766, LB26.
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: CS1 maint: multiple names: authors list (link) - ^ Getts DR, Martin A, Siemionow M, Miller SD. "Operational tolerance vs immune suppression, targeting the
α β TCR with TOL101". American Journal of Transplantation. 10 (Suppl 4 1–608, LB07).{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Lavasani S, Dzhambazov B; et al. (2007). "Monoclonal antibody against T-cell receptor alphabeta induces self-tolerance in chronic experimental autoimmune encephalomyelitis". Scandinavian Journal of Immunology. 65 (1): 39–47. doi:10.1111/j.1365-3083.2006.01866.x. PMID 17212765.
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(help) - ^ Sempe P; et al. (1991). "Anti-alpha/beta T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in non-obese diabetic (NOD) mice". Eur J Immunol. 21 (5): 1163–9. doi:10.1002/eji.1830210511. PMID 1828030.
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: Explicit use of et al. in:|author=
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