Monoclonal antibodies targeting the immune system

Scientific advances during the past decades 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 advanced melanoma (34% survival at 5 years with anti-PD-1) and non-small cell lung cancer, and proof of efficacy has been demonstrated with PD-1/PD-L1 antibodies in more than 20 cancer types in adults. By contrast, there are still limited clinical trials focusing on immunotherapies targeting the host immune system in pediatric oncology although some outstanding results have been reported in specific tumor histology/genetic predisposition syndrome. The first phase 1 in children and adolescents with recurrent/refractory solid tumors has been recently published with anti-CTL4A (ipilimumab). Toxicity profile was similar to adults and 6 (18%) of patients experienced stable disease. Translational research will allow understanding and analyzing 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 other immune checkpoints have been identified and could potentially be targeted in pediatric cancers. Future studies will help to identify predictive factors but also to coordinate these new immunotherapies with our classic treatment strategies.