Les anticorps monoclonaux dirigés contre les checkpoints immunologiques : de nouvelles approches d'immunothérapie en onco-hématologie

Scientific advances during the last years have demonstrated the critical role of host immune system in the elimination of cancer. Better knowledge of immune cancer evasion has enabled the development of new cancer immunotherapy targeted to inhibitory immune checkpoints: PD-1, PD-L1 and CTLA4. Dramatic results were obtained in melanoma (± 50% survival at 2 years with anti-PD-1) and non-small cell lung cancer and proofs of efficacy have been demonstrated with anti-PD-1/PD-L1 antibodies in more than 15 cancer types in adults. Phase 1 in children and adolescents with recurrent/refactory solid tumors has just been published with anti-CTL4A (ipilimumab). Toxicity profile was similar to adults and 6 (18%) of the patients experienced a stable disease. Translational research will allow to understand and analyze mechanisms of action of immune checkpoints regulators and define biomarkers predictive of response. These drugs are already challenging our practice like for evaluation of tumor response or for management of immune-related toxicities. Many immune checkpoints have been identified and could potentially be targeted. Future studies will help to identify predictive factors but also to coordinate these new immunotherapies with our classic treatment strategies.