Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response
| العنوان: | Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response |
|---|---|
| المؤلفون: | Keng-Chang Tsai, Tz Wen Yang, Fu Ling Chang, Yan Ni Lo, Chih Tien Chen, Tsai Yu Lin, Yu Ching Lee, Ting Sheng Chung, Wang Chuan Chen, Ming Hui Cheng, Tsung Hsun Tsai |
| المصدر: | Experimental Animals |
| بيانات النشر: | Japanese Association for Laboratory Animal Science, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | phage display technique, Phage display, Sequence analysis, medicine.drug_class, Original, medicine.medical_treatment, T-Lymphocytes, chemical and pharmacologic phenomena, Monoclonal antibody, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, molecule docking, Immune system, Cancer immunotherapy, Immunity, medicine, Animals, single-chain antibody fragment, General Veterinary, biology, Chemistry, General Medicine, V-Set Domain-Containing T-Cell Activation Inhibitor 1, Cell biology, B7-H4, biology.protein, Leukocytes, Mononuclear, Animal Science and Zoology, Antibody, immunity checkpoint protein, Chickens, Single-Chain Antibodies |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1881-7122 1341-1357 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68c70a0165d0630797cf755102694e0a http://europepmc.org/articles/PMC8390317 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....68c70a0165d0630797cf755102694e0a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18817122 13411357 |
|---|