TOL101

TOL101 is a clinical stage investigational drug. The safety and efficacy of TOL101 was the focus of a phase 2 clinical trial in renal transplant patients in 2010.^[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 multiple 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 multiple other aspects of the immune system, often resulting in long-term broad spectrum immune suppression.^[3][4] Antibodies specific for CD3 such as teplizumab and otelixizumab^[5] 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,^[6] which have been shown to play an important role in controlling viruses such as cytomegalovirus (CMV),^[7] 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]}