Allogeneic Chimeric Antigen Receptor T Cells for Hematologic Malignancies

Abstract

Autologous chimeric antigen receptor (CAR) T cell therapy has been extensively studied over the past decades. Currently, autologous CAR T products are FDA-approved to treat B cell acute lymphoblastic leukemia (B-ALL), large B cell, mantle cell, and follicular lymphomas, and multiple myeloma. However, this therapy has drawbacks including higher cost, production lead time, logistical complexity, and higher risk of manufacturing failure. Alternatively, allogeneic CAR T cell therapy, currently under clinical trial, has inherent disadvantages, including cell rejection, graft versus host disease, and undetermined safety and efficacy profiles. Different strategies, including modifying HLA and T cell receptor expression using different effector cells, are under investigation to circumvent these issues. Early allogeneic CAR T therapy results for B-ALL and B-NHL have been promising. Large sample clinical trials are ongoing. Here, we discuss the pros and cons of allo-CAR T for hematologic malignancies and review the latest data on this scalable approach.