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CAR T-cell treatment remains clinically challenging. Therapeutic strategies may be designed to cut off immunotherapy utilizing safety switches

CAR T-cell therapy still has clinical research problems. Suicide genes, combinatorial target-antigen recognition, synthetic Notch receptors, on-switch CARs, inhibitory CARs and armored CARs may all be engineered to turn off immunotherapy using safety switches. Combining CAR T-cell therapy with immunomodulatory medications such as ibrutinib, lenalidomide, or checkpoint inhibitors may extend the duration of therapeutic response. The effect of checkpoint inhibitors on infection risk is complicated and depends on pathogen, cell and organ-specific variables. The natural history of asymptomatic or moderately symptomatic COVID-19 infection is unknown, and further study is needed to evaluate if CAR T. Therapy should be postponed in individuals in severe need of possibly curative therapy. Several strategies should be used to address these research issues. These include registry studies, well-designed studies to identify infection risk factors and homogeneous populations.