期刊
MOLECULAR THERAPY-ONCOLYTICS
卷 24, 期 -, 页码 14-25出版社
CELL PRESS
DOI: 10.1016/j.omto.2021.11.018
关键词
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资金
- National Key Research and Development Plan [2018YFA0900900]
- National Natural Sci-ence Foundation of China [81872488, 81773253]
- Natural Science Foundation of Jiangsu Province [BK20161156]
- Social Development Key Project of Jiangsu Province [BE2020641, BE2016643]
- Youth Technology Innovation Team of Xuzhou Medical University [TD202003]
This study found that the combination of an oncolytic adenovirus carrying decorin and a CAR-T targeting CAIX can effectively reduce tumor burden, alter the composition of extracellular matrix, enhance CAR-T cell numbers, and improve immune responses, leading to prolonged survival in mice. These findings support further investigation of this combination therapy in solid tumors.
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-beta in tumor cells, enhanced IFN-gamma 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.
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