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

Tsai Yu Lin, Tsung Hsun Tsai, Chih Tien Chen, Tz Wen Yang, Fu Ling Chang, Yan Ni Lo, Ting Sheng Chung, Ming Hui Cheng, Wang Chuan Chen, Keng Chang Tsai, Yu Ching Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)333-343
Number of pages11
JournalExperimental Animals
Volume70
Issue number3
DOIs
Publication statusPublished - 2021

Keywords

  • B7-H4
  • Immunity checkpoint protein
  • Molecule docking
  • Phage display technique
  • Single-chain antibody fragment

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Biochemistry, Genetics and Molecular Biology(all)
  • veterinary(all)

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