Stratégies vaccinales contre le mélanome Melanoma immunotherapy

Résumé

Le mélanome est une pathologie de plus en plus fréquente, sévère, pour laquelle les traitements antitumoraux standards sont peu efficaces. Étant donné la chimiorésistance et la radiorésistance intrinsèque de cette tumeur, d’une part, et d’autre part l’existence d’un rejet spontané, certes rare, de certains mélanomes, de grands espoirs se portent sur les techniques d’immunothérapie. Le développement récent de techniques de surveillance immunologique, l’« immunomonitorage », la caractérisation de nombreux antigènes tumoraux et la découverte de cytokines nécessaires à la culture ex vivo de cellules dendritiques ont ouvert de nouvelles voies thérapeutiques. Cet article fait le point sur les différentes stratégies de vaccination contre le mélanome.

Summary

Melanoma incidence increases and conventional antitumor therapies are often ineffective, encouraging the design of novel therapies. Several lines of evidence support the notion of an immunological control of melanoma growth. Based on this information, active immunotherapy (vaccination) and adoptive immunotherapy trials (T cell therapy) were conducted in metastatic melanoma patients. The proof of principle of effective immunotherapy was brought up by pionnering trials using tumor infiltrated lymphocytes in lymphodepleted recipients or anti-CTLA4 Ab leading to tumor eradication but also autoimmune diseases. With the identification and characterization of tumor antigens recognized by cytotoxic T lymphocytes, the utilization of tumor rejection antigens along with adjuvants become available as tumor vaccines. The last five years have witnessed the emergence of dendritic cell based-vaccines that were efficient in priming and/or boosting T cell responses in normal volunteers and patients. This review highlights preclinical bases of cancer vaccines, their clinical development and discusses their limits. Correlations between immunomonitoring and tumor regressions await larger trials.