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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(03): e197-e206
DOI: 10.1055/s-0042-1755454
Original Article

Generating Anti-TIGIT and CD155 Monoclonal Antibodies for Tumor Immunotherapy

Yu-Hang Duan
1   Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China
,
Yan-lin Bian
1   Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China
,
Jian-Wei Zhu
1   Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China
› Author Affiliations Funding This research was funded by the National Natural Science Foundation of China (Grant No. 81773621 and 82073751) and the National Science and Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (Grant No. 2019ZX09732001-019).
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Abstract

Many studies have confirmed that the human poliovirus receptor (PVR; CD155) is related to tumor cell migration, invasion, and thus tumor progression. A PVR receptor binds its ligand T cell Ig and the ITIM domain (TIGIT) to inhibit the function of T and NK cells, thereby allowing tumors to evade immune surveillance. In this study, two IgG1 monoclonal antibodies, anti-CD155 and anti-TIGIT, were expressed by the mammalian transient transfection system, then, antibody-dependent cell-mediated cytotoxicity, antibody-binding affinity, and antitumor efficacy were evaluated subsequently in vitro. In this work, protein A affinity chromatography was used for antibodies' purification. Analysis methods included Western blot, enzyme-linked immunosorbent assay, and flow cytometry. Our data suggested that both the two monoclonal antibodies have a purity of higher than 90%, and bound tightly to the antigen with dissociation constant (K d) and 50% effective concentrations (EC50) below micromolar range. Most notably, these antibodies promote antitumor activity of immune cells in vitro. Therefore, our study laid down the foundation for subsequent in vivo experiments for further evaluation.

Keywords

monoclonal antibodies - TIGIT - PVR - tumor immunotherapy - antibody-dependent cell-mediated cytotoxicity

Ethics Statement

The separation of PBMCs from healthy donors abides by the relevant agreements of the Changhai Hospital of Shanghai, and it conforms to the provisions of the Declaration of Helsinki in 1995 (16). Informed consent was obtained from all individual participants included in the study.




Publication History

Received: 27 April 2022

Accepted: 13 July 2022

Article published online:
02 September 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
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