Tumor-tagging by oncolytic viruses: A novel strategy for CAR-T therapy against solid tumors

• Published in: Cancer letters 2021-04, Vol.503, p.69-74
• Main Authors: Tang, Xin-Ying, Ding, Yu-Shi, Zhou, Tao, Wang, Xu, Yang, Yong
• Format: Article
• Language: English
• Subjects: Adenoviruses; Antigens; Antitumor activity; Breast cancer; CAR-T therapy; Cell therapy; Chemokines; Chimeric antigen receptors; Design; Extracellular matrix; Heparan sulfate; Immunotherapy; Kinases; Lymphocytes; Lymphocytes T; Lymphoma; Medical research; Microenvironments; Oncolysis; Oncolytic viruses; Solid tumor; Solid tumors; Tumor microenvironment; Tumor-associated antigens; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.01.014

Chimeric antigen receptor (CAR) T cell therapy is one of the most promising immunotherapies in the past decade. It brings hope for cure to patients with previously refractory hematological malignancies. However, when translating this strategy into non-hematologic malignancies, the antitumor activity from multiple clinical studies seemed to be subtle or transient. The less satisfying efficacy in solid tumors might at least due to antigen heterogeneity, suboptimal CAR-T cell trafficking and tumor immunosuppressive environment. Here, we will review the updating strategies to challenge the therapeutic impediments of CAR-T therapy in non-hematologic malignancies. We mainly focus on the combination with oncolytic viruses (OV), the born allies for CAR-T cells. In addition to previously reported OVs-arming strategy, we discuss recently proposed tumor-tagging concept by OVs as CAR-T targets, as well as the possible improvements. Overall, tumor-tagging strategy by OVs combination with CAR-T would be a novel and promising solution for the heterogeneity and immunosuppressive microenvironment of solid tumors. •The less satisfying efficacy of CAR-T cell therapy in solid tumors might at least due to antigen heterogeneity, suboptimal CAR-T cell trafficking and tumor immunosuppressive environment.•Instead of hunting CAR-T cell targets, tagging tumor cells by oncolytic viruses (OV) provides more choices.•Oncolytic viruses can deliver novel CAR-T targets specifically to tumor cells, redirecting single-target CAR-T cells to previously antigen-mismatched tumor cells.•Adopt the gene circuit idea by inserting the RNA-based AND gate to realize better tumor-tagging specificity.