Oncolytic adenovirus-mediated expression of decorin facilitates CAIX-targeting CAR-T therapy against renal cell carcinoma

• DOI: 10.1016/j.omto.2021.11.018
• Publication Date: 2021-11-29T22:53:16Z
• Authors: Chen Zhang; Lin Fang; Xueyan Wang; Sen Yuan; Wanjing Li; Weiping Tian; Jing Chen; Qi Zhang; Yuxin Zhang; Qing Zhang; Junnian Zheng
• Keywords: 0301 basic medicine; renal cell carcinoma; 03 medical and health sciences; chimeric antigen receptor T cell; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Original Article; Decorin; RC254-282; oncolytic adenovirus; carbonic anhydrase IX; 3. Good health

Although chimeric antigen receptor T cell (CAR-T) therapy has been successful for hematological malignancies, it is less effective for solid tumors. The primary reason is that the immune microenvironment restricts CAR-T cells from infiltrating and proliferating in tumors. Oncolytic virotherapy has emerged as a novel immunogenic therapy to augment antitumor immune response. Here we combined an oncolytic adenovirus carrying decorin with a CAR-T targeting carbonic anhydrase IX (CAIX) to perform the antitumor activity for renal cancer cells. We found that OAV-Decorin combined with CAIX-CAR-T exhibited significantly reduced tumor burden, altered the composition of extracellular matrix (ECM) by inhibiting the distribution of collagen fibers, decreased the expression of TGF-β in tumor cells, enhanced IFN-γ secretion, and obtained higher numbers of CAR-T cells. The combination treatment modality showed prolonged mice survival. The intratumoral injection of OAV-Decorin into tumor-bearing immunocompetent mice activated the inflammatory immune status and resulted in tumor regression. These data supported further investigation of the combination of OAV-Decorin and CAIX-CAR-T cells in solid tumors.