A humanized TCR retaining authentic specificity and affinity conferred potent anti‐tumour cytotoxicity |
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| Authors: | Lin Chen Ye Tian Kai Zhan Anan Chen Zhiming Weng Jiao Huang Yanyan Li Yongjie Sun Hongjun Zheng Yi Li |
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| Affiliation: | 1. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China;2. University of Chinese Academy of Sciences, Beijing, China;3. XiangXue Life Sciences Research Center, XiangXue Pharmaceutical Co. Ltd, Guangzhou, China;4. School of Life Sciences, University of Science and Technology of China, Hefei, China;5. Institute of Health Sciences, Anhui University, Hefei, China |
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| 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‐A3112–120 (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. |
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| Keywords: | activation humanized TCR immunogenicity murine TCR T‐cell |
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