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

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. Beca...

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Bibliographic Details
Published in:BMC biotechnology 2022-08, Vol.22 (1), p.1-22, Article 22
Main Authors: Ghaderi, Sepideh Safaei, Riazi-Rad, Farhad, Qamsari, Elmira Safaie, Bagheri, Salman, Rahimi-Jamnani, Fatemeh, Sharifzadeh, Zahra
Format: Article
Language:English
Subjects:
Anticancer properties
Antigens
Antitumor agents
Autoimmune diseases
Cancer
Care and treatment
Cytokines
Dendritic cells
E coli
Genetic aspects
Growth factors
Health aspects
Immune checkpoint
Immune checkpoint inhibitor
Immune response
Immunotherapy
Infectious diseases
Interleukin 2
Ir genes
Kinases
Ligands
Lymphocytes
Lymphocytes T
Monoclonal antibodies
Panning
PD-1
PD-1 protein
PD-L1 protein
Phage display
Phages
Proteins
Single-chain fragment antibody
T cells
Tumor cells
Tumor microenvironment
Tumors
Viruses
γ-Interferon
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Summary: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. 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-[gamma] by Jurkat T cells that were co-cultured with PD-L1 positive tumor cells. 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
1472-6750
DOI:10.1186/s12896-022-00752-8