跳至主要内容

A humanized TCR retaining authentic specificity and affinity conferred potent antitumour cytotoxicity

Author：Lin Chen, Ye Tian, Kai Zhan, Anan Chen, Zhiming Weng, Jiao Huang, Yanyan Li, Yongjie Sun, Hongjun Zheng, Yi Li   《Immunology》

ABSTRACTS
The affinity of Tcell receptor (TCR) determines the efficacy of TCRbased immunotherapy. By using human leucocyte antigen (HLA)A*02 transgenic mice, a TCR was generated previously specific for human tumour testis antigen peptide MAGEA3112–120 (KVAELVHFL) HLAA*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 antitumour activity than its parent murine MAGEA3 TCR (SRm1). In addition, the affinity of humanized TCR was enhanced further to achieve improved Tcell activation. Our studies demonstrated that the human TCR variable domain frameworks could provide support for complementaritydetermining regions from a murine TCR, and retain the original binding activity. It could be used as a generic approach of TCR humanization.
SCREENSHOT

RELATED PRODUCTS
The MAGE-A3 peptide (KVAELVHFL) (ChinaPeptides) 
CHAINING
https://onlinelibrary.wiley.com/doi/full/10.1111/imm.12935
标签：

评论

发表评论

此博客中的热门博文

The Catalytically Inactive Mutation of the Ubiquitin-Conjugating Enzyme CDC34 Affects its Stability and Cell Proliferation

Author：Xun Liu, Yang Zhang, Zhanhong Hu, Qian Li, Lu Yang,  Guoqiang Xu     《The Protein Journal》 ABSTRACTS The ubiquitin proteasome system (UPS) plays important roles in the regulation of protein stability, localization, and activity. A myriad of studies have focused on the functions of ubiquitin ligases E3s and deubiquitinating enzymes DUBs due to their specificity in the recognition of downstream substrates. However, the roles of the most ubiquitin-conjugating enzymes E2s are not completely understood except that they transport the activated ubiquitin and form E2–E3 protein complexes. Ubiquitin-conjugating enzyme CDC34 can promote the degradation of downstream targets through the UPS whereas its non-catalytic functions are still elusive. Here, we find that mutation of the catalytically active cysteine to serine (C93S) results in the reduced ubiquitination, increased stability, and attenuated degradation rate of CDC34. Through semi-quantitative proteom...
发表评论
阅读全文

A Quasi-direct LC-MS/MS-based Targeted Proteomics Approach for miRNA Quantification via a Covalently Immobilized DNA-peptide Probe

Author：Liang Liu, Qingqing Xu, Shuai Hao & Yun Chen     《Scientific Reports》 ABSTRACTS MicroRNAs (miRNAs) play a vital role in regulating gene expression and are associated with a variety of cancers, including breast cancer. Their distorted and unique expression is a potential marker in clinical diagnoses and prognoses. Thus, accurate determination of miRNA expression levels is a prerequisite for their applications. However, the assays currently available for miRNA detection typically require pre-enrichment, amplification and labeling steps, and most of the assays are only semi-quantitative. Therefore, we developed a quasi-direct liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics approach to quantify target miRNA by innovatively converting the miRNA signal into the mass response of a reporter peptide  via  a covalently immobilized DNA-peptide probe. Specifically, the probe containing the targeted proteomics-...
发表评论
阅读全文

Preparation of an antimicrobial surface by direct assembly of antimicrobial peptide with its surface binding activity

Author：Junjian Chen, Yuchen Zhu, Yancheng Song, Lin Wang,  Jiezhao Zhan, Jingcai He, Jian Zheng, Chunting Zhong, Xuetao Shi, Sa Liu, Li Ren and Yingjun Wang     《Journal of Materials Chemistry B》 ABSTRACTS Antimicrobial peptides (AMPs) are a broad prospect for clinical application against bacterial infections of biomaterials. However, a bottleneck exists as there is a lack of simple technology to prepare AMPs on biomaterials with sufficient activity, as the activity of AMP is dependent on the correct orientation on the biomaterial. In the present study, based on the conventional AMP (Tet213: KRWWKWWRRC) and surface binding peptide (SKHKGGKHKGGKHKG), we designed an Anchor-AMP that could be directly assembled onto the surface of the biomaterial and also showed excellent antimicrobial activity. By characterizing the surface using a quartz crystal microbalance with dissipation (QCM-D), contact angle, atom force microscopy (AFM) and X-ray photoelectron spectr...
发表评论
阅读全文