Engineering enhanced chimeric antigen receptor-T cell therapy for solid tumors

The early clinical success and subsequent US Food and Drug Administration approval of chimeric antigen receptor (CAR)-T cell therapy for leukemia and lymphoma affirm that engineered T cells can be a powerful treatment for hematologic malignancies. Yet this success has not been replicated in solid tumors. Numerous challenges emerged from clinical experience and well-controlled preclinical animal models must be met to enable safe and efficacious CAR-T cell therapy in solid tumors. Here, we review recent advances in bioengineering strategies developed to enhance CAR-T cell therapy in solid tumors, focusing on targeted single-gene perturbation, genetic circuits design, cytokine engineering, and interactive biomaterials. These bioengineering approaches present a unique set of tools that synergize with CAR-T cells to overcome obstacles in solid tumors and achieve robust and long-lasting therapeutic efficacy.