Development of a human phage display-derived anti-PD-1 scFv antibody: an attractive tool for immune checkpoint therapy

Abstract Background The PD-1 checkpoint pathway plays a major role in tumor immune evasion and the development of the tumor microenvironment. Clinical studies show that therapeutic antibodies blocking the PD-1 pathway can restore anti-tumor or anti-virus immune responses by the reinvigoration of exh...

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Bibliographic Details
Main Authors: Sepideh Safaei Ghaderi, Farhad Riazi-Rad, Elmira Safaie Qamsari, Salman Bagheri, Fatemeh Rahimi-Jamnani, Zahra Sharifzadeh
Format: Article
Language:English
Published: BMC 2022-08-01
Series:BMC Biotechnology
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Online Access:https://doi.org/10.1186/s12896-022-00752-8
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Summary:Abstract Background The PD-1 checkpoint pathway plays a major role in tumor immune evasion and the development of the tumor microenvironment. Clinical studies show that therapeutic antibodies blocking the PD-1 pathway can restore anti-tumor or anti-virus immune responses by the reinvigoration of exhausted T cells. Because of the promising results of anti-PD-1 monoclonal antibodies in cancer treatment, autoimmune disorders, and infectious diseases, the PD-1 has emerged as an encouraging target for different diseases. Results In the present study, we employed a human semi-synthetic phage library for isolation of some scFvs against the extracellular domain of PD-1 protein by panning process. After the panning, a novel anti-PD-1 scFv (SS107) was found that exhibited specific binding to PD-1 antigen and stimulated Jurkat T cells. The selected anti-PD-1 scFv could restore the production of IL-2 and IFN-γ by Jurkat T cells that were co-cultured with PD-L1 positive tumor cells. Conclusion This anti-PD-1 scFv with high specificity and the ability to reactivate exhausted T cells has the potential to be developed as an anti-cancer agent or to be used in combination with other therapeutic approaches.
ISSN:1472-6750