Combining Oncolytic Viruses With Chimeric Antigen Receptor T Cell Therapy

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematological malignancies, but solid tumors continue to pose significant challenges. Oncolytic viruses (OVs) have generated significant excitement in the field of cancer treatment recently. In particular, OVs can help CAR T cells overcome some of the immunosuppressive mechanisms within the tumor microenvironment through OV intrinsic effects or delivery of immunostimulatory agents. Numerous preclinical studies demonstrate that combining CAR T cells with OVs can increase CAR T cell trafficking, antitumor activity, and elimination of antigen-negative tumor cells. Despite promising preclinical results, only one clinical trial (NCT03740256) investigating CAR T and OV combination therapy is underway, highlighting the challenges of translating this approach to the clinic. Antiviral immunity and the route of OV administration, in addition to concerns about cost and safety, limit the clinical application of this approach. Strategies to reduce the production cost of both CAR T cells and OVs, as well as molecularly modifying OVs to enhance their bioavailability, will likely encourage further exploration of this combination therapy in clinical trials.