Versatile CAR T-cells for cancer immunotherapy

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has been clinically proven to efficiently combat haematological malignancies. However, continuous efforts are required to increase the specificity of CAR T-cells against tumour versus normal tissues, and are essential to improve their antitumour activity in solid tumours. This review summarises the structure of major CAR designs, and strategies to overcome immunosuppressive tumour microenvironment, and reduce toxicities. Along with reviewing currently available techniques that allow the elimination of CAR T-cells after they fulfil their desired functions, using suicide genes, drug elimination strategies are also introduced. A better understanding of the strengths and pitfalls of CAR T-cell therapy will provide fundamental knowledge for the improvement of engineered T-cell therapy in the near future.

Keywords: CAR T-cell therapy; chimeric antigen receptor; haematological and solid tumors.

Fig. 1

Chimeric antigen receptor (CAR) structure and design. A) Three generations of CARs. CAR compromises 3 domains: extracellular domain; transmembrane domain; and cytoplasmic domain. First generation CAR only has CD3ζ domain; second-generation CAR incorporates CD28 or 4-1BB, while the third-generation CAR incorporates both or more. B) Primary CARs design and evolution