Chemistry

Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer

P. A. Szijj, M. A. Gray, et al.

Discover groundbreaking research from Peter A. Szijj, Melissa A. Gray, Mikaela K. Ribi, Calise Bahou, João C. F. Nogueira, Carolyn R. Bertozzi, and Vijay Chudasama, highlighting a cutting-edge chemical method for creating biotin-functionalized checkpoint inhibitory T cell engagers (CiTEs). This innovative approach enhances T cell-mediated cancer cell death more effectively than traditional methods, offering rapid and flexible solutions for multi-protein constructs.

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Abstract

This paper describes a chemical method for generating biotin-functionalized three-protein conjugates, termed checkpoint inhibitory T cell engagers (CiTEs), which combine bispecific T cell engager (BiTE) technology with an immunomodulatory protein to enhance cancer cell death. The CiTEs demonstrated superior efficacy compared to BiTEs *in vitro*, particularly those containing *Salmonella typhimurium* sialidase, significantly enhancing T cell-mediated cytotoxicity. This chemical approach offers greater modularity and speed than traditional protein engineering methods for generating multi-protein constructs with various biological applications.

Publisher

Nature Chemistry

Published On

Jul 24, 2023

Authors

Peter A. Szijj, Melissa A. Gray, Mikaela K. Ribi, Calise Bahou, João C. F. Nogueira, Carolyn R. Bertozzi, Vijay Chudasama

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