Académie royale de Médecine de Belgique

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Vidéo et résumé de B. Van den Eynde et J.-Fr. Baurain

 

SYMPOSIUM CONSACRÉ AU MÉLANOME EN DATE DU 6 OCTOBRE 2012

 

IMMUNOTHERAPY OF MELANOMA : RESULTS AND PERSPECTIVES  

par B. VAN den EYNDE (UCL), membre titulaire et J.-Fr. BAURAIN (UCL), coll.         

Melanoma is an antigenic and immunogenic tumor. It carries various antigens that are absent or highly restricted on normal tissues, and it elicits spontaneous immune responses mediated by T lymphocytes. Several strategies have been developed to make use of these features to treat patients with metastatic disease. Vaccines comprising tumor antigens aimed at inducing anti-melanoma T lymphocyte responses have been investigated in numerous clinical trials. These vaccines were well tolerated, and showed some anti-tumoral effects, however limited to a small minority of patients. It is likely that many melanomas acquire the ability to resist immune destruction during their evolution, which might explain the low efficacy of cancer vaccines. New treatments that restore T cell activity in tumors are now emerging. Ipilimumab (Yervoy®) is a humanized antibody that blocks CTLA-4, a protein that becomes expressed on T lymphocytes upon activation and acts as a negative feedback by inhibiting continuous T cell activation. This drug was recently shown to increase the survival of patients with metastatic melanoma, but it also causes severe toxicities consistent with autoimmune reactions. It was recently approved by the FDA and EMA, and is reimbursed in Belgium since June 2012. Very recently, antibodies targeting PD-1 and PD-L1, two molecules involved in a similar inhibitory T cell pathway, showed encouraging clinical results. The possible advantage of combining immune therapies with each other and with other treatments such as specific pathway inhibitors remains to be investigated. Our group has contributed to the field by identifying many tumor antigens and investigating cancer vaccines in the clinic, and is now focused on the characterization of tumor resistance to immune destruction and on possible means to counteract it.

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