Chimeric antigen receptor (CAR)-T-cell therapies have shown remarkable clinical efficacy in hematological malignancies. However, objective clinical responses in solid tumors are limited. Various obstacles, such as the lack of ideal tumor-specific antigens and the immunosuppressive tumor microenvironment (TME), which impairs multiple immunological steps required to achieve effective cancer control, compromise the antitumor efficacy of CAR-T-cell therapy in solid tumors. To address this issue, combination treatment with oncolytic viruses (OVs) and CAR-T cells is being explored. OVs can modulate immunosuppression in the TME and invigorate both endogenous and adoptively transferred T cells, in addition to directly killing tumor cells. The immunomodulatory effect is further augmented by the use of OVs with therapeutic transgenes as payloads. Many preclinical evaluations have provided promising evidence for the combination approach, and clinical studies are ongoing. In this review, the mechanisms underlying resistance to CAR-T-cell therapies and recent advances in combination therapy with OVs and CAR-T cells are discussed from the perspective of the cancer-immunity cycle.
Watanabe et al. (Fri,) studied this question.