Strategies for overcoming bottlenecks in allogeneic CAR-T cell therapy

Abstract

Patient-derived autologous chimeric antigen receptor (CAR)-T cell therapy is a revolutionary breakthrough in immunotherapy and has made impressive progress in both preclinical and clinical studies. However, autologous CAR-T cells still have notable drawbacks in clinical manufacture, such as long production time, variable cell potency and possible manufacturing failures. Allogeneic CAR-T cell therapy is significantly superior to autologous CAR-T cell therapy in these aspects. The use of allogeneic CAR-T cell therapy may provide simplified manufacturing process and allow the creation of 'off-the-shelf' products, facilitating the treatments of various types of tumors at less delivery time. Nevertheless, severe graft-versus-host disease (GvHD) or host-mediated allorejection may occur in the allogeneic setting, implying that addressing these two critical issues is urgent for the clinical application of allogeneic CAR-T cell therapy. In this review, we summarize the current approaches to overcome GvHD and host rejection, which empower allogeneic CAR-T cell therapy with a broader future.

Keywords: T cell subsets; allogeneic CAR-T cell; gene-editing technology; non-gene editing technology; pluripotent stem cell.