A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma

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• 作者：Tong Wang ; Fumou Sun ; Wei Xie ; Mingying Tang ; Hua He ; Xuelian Jia ; Xuemei Tian ; Min Wang ; ^{minwang@cpu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Juan Zhang ; ^{juancpu@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Antibody fusion protein ; CD24 ; MICA ; NK cells ; Immunosurveillance
• 刊名：Cancer Letters
• 出版年：2016
• 出版时间：28 March 2016
• 年：2016
• 卷：372
• 期：2
• 页码：166-178
• 全文大小：5784 K

文摘

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.