期刊
CANCER LETTERS
卷 372, 期 2, 页码 166-178出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.01.001
关键词
Antibody fusion protein; CD24; MICA; NK cells; Immunosurveillance
类别
资金
- National Natural Science Foundation of China [NSFC81473125]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Graduate Innovation Program of Jiangsu Province [KYLX15_0670]
- Undergraduate Training Program of Jiangsu Province for Innovation and Entrepreneurship [SY15090]
MHC class I-related chain A (MICA) is a principal immunoligand of the natural killer (NK) cell receptor NK group 2, member D (NKG2D) and plays a key role in NK cell-mediated immune recognition. Shedding of MICA from tumor cells leads to immunosuppression. To reconstitute the immunosurveilance function of NK cells, we constructed a fusion protein rG7S-MICA and explored its potential anti-tumor activity against hepatocellular carcinoma (HCC). rG7S-MICA consists of human MICA and a single-chain antibody fragment (scFv) targeting the tumor-associated antigen cluster of differentiation 24 (CD24). In vitro, rG7S-MICA engaged both NK cells and CD24(+) human HCC cells, and triggered NK cell-mediated cytolysis. Furthermore, in CD24(+) HCC-bearing nude mice, rG7S-MICA specifically targeted to the tumor tissue, where it effectively recruited NK cells and induced the release of cytokines, and showed superior antitumor activity. In conclusion, rG7S-MICA provides a new approach for HCC-targeting immunotherapy and has attracting potentials for clinical applications. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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