A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma. Issue 2 (28th March 2016)

• Record Type: Journal Article
• Authors: Wang, Tong; Sun, Fumou; Xie, Wei; Tang, Mingying; He, Hua; Jia, Xuelian; Tian, Xuemei; Wang, Min; Zhang, Juan
• Is Part Of: Cancer letters. Volume 372:Issue 2(2016)
• Page Start: 166
• Page End: 178
• Publication Date: 2016-03-28
• Subjects: Antibody fusion protein -- CD24 -- MICA -- NK cells -- Immunosurveillance; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.01.001
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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 anti-tumor activity. In conclusion, rG7S-MICA provides a new approach for HCC-targeting immunotherapy and has attracting potentials for clinical applications.