How Can We Engineer CAR T Cells to Overcome Resistance?

Abstract

Chimeric antigen receptor (CAR) T cell therapy has achieved unrivalled success in the treatment of B cell and plasma cell malignancies, with five CAR T cell products now approved by the US Food and Drug Administration (FDA). However, CAR T cell therapies for solid tumours have not been nearly as successful, owing to several additional challenges. Here, we discuss mechanisms of tumour resistance in CAR T cell therapy and the emerging strategies that are under development to engineer CAR T cells to overcome resistance.

Keywords:

• chimeric antigen receptor
• cancer
• immunotherapy
• T-cell
• resistance

Acknowledgments

Research in JM’s laboratory is supported by Leucid Bio, Breast Cancer Now, British Lung Foundation, the Wellcome Trust, the J P Moulton Charitable Foundation, the Medical Research Council, the King’s Health Partners Research and Development Fund, the Experimental Cancer Medicine Centre at King’s College London, the Cancer Research UK Centre at King’s Health Partners and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Disclosure

JM is founder, chief scientific officer and shareholder in Leucid Bio. MG is an employee and shareholder in Leucid Bio. The authors report no other conflicts of interest in this work.