T cells modified via chimeric antigen receptors (CARs) have emerged as a promising treatment modality. Unparalleled clinical efficacy recently demonstrated in refractory B-cell malignancy has brought this new form of adoptive immunotherapy to the center stage. Nonetheless, its current success has also highlighted its potential treatment-related toxicities. The adverse events observed in the clinical trials are described in this review, after which, some innovative strategies developed to overcome these unwanted toxicities are outlined, including suicide genes, targeted activation, and other novel strategies.

T-cell therapy using genetically engineered T cells modified with either T cell receptor or chi-meric antigen receptor holds great promise for cancer immunotherapy. The concerns about its toxicities still remain despite recent successes in clinical trials. Temporal and spatial control of the engineered therapeutic T cells may improve the safety profile of these treatment regimens. To achieve these goals, numerous approaches have been tested and utilized including the incorporation of a suicide gene, the switch-mediated activation, the combinatorial antigen recognition, etc. This review will summarize the toxicities caused by engineered T cells and novel strategies to overcome them.

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