Journal
CELLULAR IMMUNOLOGY
Volume 348, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2020.104041
Keywords
Chimeric antigen receptor modified T cells; Oncolytic adenovirus; Mesothelin; Transforming growth factor; Breast cancer
Categories
Funding
- National Key Research and Development Program of China [2017YFC1200503]
- Key Research and Development Program of Heibei Province [19272405D]
- Nova Program of Beijing [Z171100001117118]
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Chimeric antigen receptor (CAR)-modified T cell therapy evokes only modest antitumor responses in solid tumors. Meso-CAR-T cells are CAR-T cells targeted mesothelin, which are over-expressed in tumor tissues of breast cancer patients. To improve the therapeutic effects, we combined it with rAd.sT, a transforming growth factor ji signaling-targeted oncolytic adenovirus, to therapy breast cancer. In subcutaneous MDA-MB-231 xenograft of NSG mice, both rAd.sT and meso-CAR-T inhibited tumor growth, however combination therapy produced stronger inhibitory effects. Interestingly, rAd.sT reduced tumor burden at initial stage following vector treatments, while meso-CAR-T cells decreased tumor burden at a later stage. Moreover, meso-CAR-T could target tumor microenvironments, and combination therapy could enhance cytokines production, such as interleukin (IL)-6 and IL-12 in tumor microenvironment. In conclusion, combination of rAd.sT with meso-CAR-T produced much more impressive antitumor responses to breast cancer and its metastasis, which could be developed as a promising therapeutic strategy.
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