A Humanized TCR Retaining Authentic Specificity and Affinity Conferred Potent Anti-tumour Cytotoxicity

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2018 Apr 13

PMID 29645087

Citations 1

Authors

Lin Chen

Ye Tian

Kai Zhan

Anan Chen

Zhiming Weng

Jiao Huang

Yanyan Li

Yongjie Sun

Hongjun Zheng

Yi Li

Affiliations

Soon will be listed here.

Abstract

The affinity of T-cell receptor (TCR) determines the efficacy of TCR-based immunotherapy. By using human leucocyte antigen (HLA)-A*02 transgenic mice, a TCR was generated previously specific for human tumour testis antigen peptide MAGE-A3 (KVAELVHFL) HLA-A*02 complex. We developed an approach to humanize the murine TCR by replacing the mouse framework with sequences of folding optimized human TCR variable domains for retaining binding affinity. The resultant humanized TCR exhibited higher affinity and conferred better anti-tumour activity than its parent murine MAGE-A3 TCR (SRm1). In addition, the affinity of humanized TCR was enhanced further to achieve improved T-cell activation. Our studies demonstrated that the human TCR variable domain frameworks could provide support for complementarity-determining regions from a murine TCR, and retain the original binding activity. It could be used as a generic approach of TCR humanization.

Citing Articles

A Nobel Prize-worthy pursuit: cancer immunology and harnessing immunity to tumour neoantigens.

Altmann D Immunology. 2018; 155(3):283-284.

PMID: 30320408 PMC: 6187215. DOI: 10.1111/imm.13008.

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