Early-phenotype CAR-T cells for the treatment of pediatric cancers
Cet article présente les différentes stratégies pour maintenir in vitro des lymphocytes CAR-T à un stade faiblement différencié puis passe en revue les données mettant en évidence la pertinence de ce type de lymphocytes CAR-T pour traiter un cancer pédiatrique
Chimeric antigen receptor (CAR) T cell therapy is a promising approach for the treatment of childhood cancers, particularly high-risk tumors that fail to respond to standard therapies. CAR-T cells have been highly successful in treating some types of hematological malignancies. However, CAR-T cells targeting solid cancers have had limited success so far for multiple reasons, including their poor long-term persistence and proliferation. Evidence is emerging to show that maintaining CAR-T cells in an early, less differentiated state in vitro results in superior persistence, proliferation, and anti-tumor effects in vivo. Children are ideal candidates for receiving less-differentiated CAR-T cells, because their peripheral T cell pool primarily comprises naïve cells that could readily be harvested in large numbers to generate early-phenotype CAR-T cells. Although several studies have reported different approaches to successfully generate early CAR-T cells, there are only a few clinical trials testing these in adult patients. No trials are currently testing early CAR-T cells in children. Here, we summarize the different strategies used to maintain CAR-T cells in an early phenotypic stage, and present evidence suggesting that this approach may be particularly relevant to treating childhood cancers.
Annals of Oncology , résumé, 2021