The role of chimeric antigen receptor T cells targeting more than one antigen in the treatment of B‐cell malignancies

Abstract

SummarySeveral products containing chimeric antigen receptor T cells targeting CD19 (CART19) have been approved for the treatment of patients with relapsed/refractory non‐Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL). Despite very impressive response rates, a significant percentage of patients experience disease relapse and die of progressive disease. A major cause of CART19 failure is loss or downregulation of CD19 expression in tumour cells, which has prompted a myriad of novel strategies aimed at targeting more than one antigen (e.g. CD19 and CD20 or CD22). Dual targeting can the accomplished through co‐administration of two separate products, co‐transduction with two different vectors, bicistronic cassettes or tandem receptors. In this manuscript, we review the pros and cons of each strategy and the clinical results obtained so far.

Optimisation de l’efficacité et de la sécurité d’utilisation des lymphocytes CAR-T

“…[28]. Pour pallier ce problème récurrent dans les essais cliniques impliquant les CAR-T, il est maintenant possible de créer des CAR-T qui expriment deux récepteurs chimériques distincts ayant des cibles différentes, CD19 et CD22 par exemple [28,29]. Ces CAR-T dites bicistroniques sont de plus en plus utilisés dans les essais cliniques, notamment ceux visant des tumeurs solides.…”