Target Validation Information
Target ID T15000
Target Name Cytotoxic T-lymphocyte protein 4
Target Type
Successful
Drug Potency against Target Tremelimumab Drug Info IC50 = 0.5~0.65 nM
Action against Disease Model Tremelimumab Tremelim uMab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells. Tremelim uMab enhanced the proliferative response of T effector cells (Teff) upon TCR stimulation, and abrogated Treg suppressive ability. In the presence of tremelim uMab, frequencies of IL-2-secreting CD4(+) T cells and IFN-|??secreting CD4(+) and CD8(+) T cells were increased in response to polyclonal activation and t uMor antigens. [553079] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations The critical homeostasis mediated by CTLA-4 was proven using monoclonal antibodies and genetically disrupted CTLA-4 knockout mice that develop polyclonal lymphocyte activation and proliferation leading to massively enlarged lymph nodes and spleen and fatal multiorgan lymphocytic infiltrates. CTLA-4 ligation following T-cell activation downregulates cytokine production and cell-cycle progression, however, the proximal biochemical basis for robust T-cell regulation remains unclear. In this review, we s uMmarize studies supporting a dynamic role for CTLA-4 at the immunological synapse leading to direct attenuation of early cell signals. A model is proposed based on these observations, which proposes that CTLA-4 may, in fact, function under some circ uMstances in a ligand-independent manner. [553079]
References
Ref 553079Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells. Clin Immunol. 2011 Jan;138(1):85-96. doi: 10.1016/j.clim.2010.09.011. Epub 2010 Nov 5.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.