Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

Autor:	Tang X; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China., He L; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China., Wang X; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China., Liu S; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China.; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China., Liu X; Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University & Department of Stomatology, College of Stomatology, Jinan University, Guangzhou, China., Shen X; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China., Shu Y; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China., Yang K; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China., Zhou Q; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China., Shan Z; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China., Wang Y; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China., Wu C; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China., Jia Z; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China., Liu T; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China., Wang Y; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China., Liao HX; Zhuhai Trinomab Pharmaceutical Co., Ltd, Zhuhai, Guangdong, China., Xia Y; The People's Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan, China.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Aug 03; Vol. 10 (15), pp. e35697. Date of Electronic Publication: 2024 Aug 03 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e35697
Abstrakt:	Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction. Competing Interests: Patent application by Trinomab for anti-MICA/B mAbs used in the study is pending. All authors declare no potential conflicts of interests. (© 2024 The Authors.)
Databáze:	MEDLINE
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