Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response

doi:10.1538/expanim.20-0178

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23456

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题名:	Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response
作者:	Lin, TY;Tsai, TH;Chen, CT;Yang, TW;Chang, FL;Lo, YN;Chung, TS;Cheng, MH;Chen, WC;Tsai, KC;Lee, YC
关键词:	B7-H4;immunity checkpoint protein;molecule docking;phage display technique;single-chain antibody fragment
日期:	2021
上传时间:	2022-08-05T09:37:35Z (UTC)
出版者:	INT PRESS EDITING CENTRE INC
ISSN:	1341-1357
摘要:	For highly conserved mammalian protein, chicken is a suitable immune host to generate antibodies. Monoclonal antibodies have been successfully targeted with immunity checkpoint proteins as a means of cancer treatment; this treatment enhances tumor-specific immunity responses through immunoregulation. Studies have identified the importance of B7-H4 in immunoregulation and its use as a potential target for cancer treatment. High levels of B7-H4 expression are found in tumor tissues and are associated with adverse clinical and pathological characteristics. Using the phage display technique, this study isolated specific single-chain antibody fragments (scFvs) against B7-H4 from chickens. Our experiment proved that B7-H4 clearly induced the inhibition of T-cell activation. Therefore, use of anti-B7-H4 scFvs can effectively block the exhaustion of immunity cells and also stimulate and activate T-cells in peripheral blood mononuclear cells. Sequence analysis revealed that two isolated scFv S2 and S4 have the same VH complementarity-determining regions (CDRs) sequence. Molecule docking was employed to simulate the complex structures of scFv with B7-H4 to analyze the interaction. Our findings revealed that both scFvs employed CDR-H1 and CDR-H3 as main driving forces and had strong binding effects with the B7-H4. The affinity of scFv S2 was better because the CDR-L2 loop of the scFv S2 had three more hydrogen bond interactions with B7-H4. The results of this experiment suggest the usefulness of B7-H4 as a target for immunity checkpoints; the isolated B7-H4-specific chicken antibodies have the potential for use in future cancer immunotherapy applications.
URI:	http://dx.doi.org/10.1538/expanim.20-0178 https://www.webofscience.com/wos/woscc/full-record/WOS:000716629800007 https://ir.csmu.edu.tw:8080/handle/310902500/23456
關聯:	EXPERIMENTAL ANIMALS ,2021,v70,issue 3, P333-343
显示于类别:	[中山醫學大學研究成果] 期刊論文

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