Activation of T lymphocytes is due to their stimulation by presentation of the Ag (carried by the major histocompatibility complex MHC) to the TCR (T cell receptor), but also to a co-stimulation by APC (antigen presenting cell) membrane glycoproteins CD 80 and CD 86. Both act on the T lymphocyte :
- on the CD 28 receptor, which co-activates it
- on the CTLA-4 / CD152 (cytotoxic lymphocyte associated antigen), which inhibits this activation, but a bit later.
- IPILIMUMAB / MDX010 (IgG1) & TREMELIMUMAB (IgG2**), the fully human anti CTLA-4 monoclonals
Contrarywise to CTLA-4-Igs, essentially immunosuppressant, Ipilimumab & Ticilimumab, the fully human anti CTLA-4 monoclonals, block lymphocyte inhibition due to CTLA-4 , and thus enhance the anticancer immune defences. An ongoing trial associating Ipilimumab & GVAXimmunotherapy (prostate cancer cell lines that have been modified to secrete GM-CSF) showed promising data at ASCO Prostate in February 2007.