Allogeneic chimeric antigen receptor cell therapies for cancer: progress made and remaining roadblocks

Abstract

Chimeric antigen receptor (CAR) T cells are revolutionizing cancer therapy, particularly for haematological malignancies, conferring durable and sometimes curative responses in patients with advanced-stage disease. The CAR T cell products currently approved for clinical use are all autologous and are often effective; however, in patients who are lymphopenic and/or heavily pretreated with chemotherapy, autologous T cells can be difficult to harvest in sufficient numbers or have functional impairments that might ultimately render them less efficacious. Moreover, autologous products take several weeks to produce, and each product can be used in only one patient. By contrast, allogeneic CAR T cells can be produced for many patients using T cells from a single healthy donor, can be optimized for safety and efficacy, can be instantly available for ‘off-the-shelf’ use and, therefore, might also be more cost-effective. Despite these potential advantages, the development of allogeneic CAR T cells has lagged behind that of autologous products, owing to the additional challenges such as avoiding graft-versus-host disease and host-mediated graft rejection. Over the past few years, the development of advanced genome-editing techniques has facilitated the generation of novel allogeneic CAR T cell products. Furthermore, CAR cell products derived from other cell types such as induced pluripotent stem cells and natural killer cells are being investigated for clinical use. In this Review, we discuss the potential of allogeneic CAR cell products to expand life-saving immunotherapy to a much broader population of patients in the coming years, the progress made to date and strategies to overcome remaining hurdles.