期刊
MOLECULAR THERAPY-ONCOLYTICS
卷 17, 期 -, 页码 180-189出版社
CELL PRESS
DOI: 10.1016/j.omto.2020.03.019
关键词
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资金
- National Natural Science Foundation of China [31471286]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2019ZX09301-147]
- 1.3.5 Project for Disciplines of Excellence of the West China Hospital, Sichuan University [ZYJC18007]
- Major Subject of the Science and Technology Department of Sichuan Province [2017SZ0015, 2019YFS0108]
Recently, B7-H3 was frequently reported to be overexpressed in various cancer types and has been suggested to be a promising target for cancer immunotherapy. In the present study, we analyzed the mRNA expression of B7-H3 in The Cancer Genome Atlas (TCGA) database and validated its expression across multiple cancer types. We then generated a novel B7-H3-targeted chimeric antigen receptor (CAR) and tested its antitumor activity both in vitro and in vivo. The B7-H3 expression heterogeneity and variation were frequent. Moderate or even high expression levels of B7-H3 were also observed in some tumor-adjacent tissues, but the staining intensity was weaker than that in tumor tissues. B7-H3 expression was absent or very low in normal tissues and organs. Flow cytometry indicated that the mean expression level of B7-H3 in eight bone marrow specimens from patients with acute myeloid leukemia (AML) was 57.2% (range 38.8-80.4). Furthermore, we showed that the B7-H3-targeted CAR-T cells exhibited significant antitumor activity against AML and melanoma in vitro and in xenograft mouse models. In conclusion, although B7-H3 represents a promising pan-cancer target, and B7-H3-redirected CAR-T cells can effectively control tumor growth, the expression heterogeneity and variation have to be carefully considered in translating B7-H3-targeted CAR-T cell therapy into clinical practice.
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