Oncolytic adenovirus-mediated expression of CCL5 and IL12 facilitates CA9-targeting CAR-T therapy against renal cell carcinoma

• DOI: 10.1016/j.phrs.2023.106701
• Publication Date: 2023-02-14T21:37:48Z
• Authors: Lin Fang; Weiping Tian; Chen Zhang; Xueyan Wang; Wanjing Li; Qi Zhang; Yuxin Zhang; Junnian Zheng
• Keywords: Oncolytic adenovirus; CCL5

Chimeric antigen receptor T-cell (CAR-T) is particularly prominent in hematological but not solid tumors, mainly based on the complex tumor immune microenvironment. Oncolytic virus (OVs) an emerging adjuvant therapy method. OVs may prime lesions to induce anti-tumor response, thereby enhancing CAR-T cells functionality and possibly increasing response rates. Here, we combined targeting carbonic anhydrase 9 (CA9) oncolytic adenovirus (OAV) carrying chemokine (C-C motif) ligand 5 (CCL5), cytokine interleukin-12 (IL12) explore effects of this combination strategy. The data showed that Ad5-ZD55-hCCL5-hIL12 could infect replicate renal cancer cell lines induced a moderate inhibition xenografted nude mice. IL12 mediated by promoted phosphorylation Stat4 cells, secrete more IFN-γ. We also found Ad5-ZD55-hCCL5-hIL-12 with CA9-CAR-T significantly increased infiltration mass, prolonged survival mice restrained growth immunodeficient Ad5-ZD55-mCCL5-mIL-12 increase CD45+CD3+T prolong immunocompetent These results provided feasibility for which demonstrated sufficient potential prospects treatment tumors.