mage-a3 humanized T cell receptor

A technology of MAGE-A3 and cell receptors, which is applied to cells modified by introducing foreign genetic material, receptors/cell surface antigens/cell surface determinants, viruses/bacteriophages, etc., can solve the problem of reduced affinity for antigen recognition

Active Publication Date: 2021-03-30
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although CDR transplantation retains the ability to recognize antigens, the affinity for antigens is often reduced

Method used

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  • mage-a3 humanized T cell receptor
  • mage-a3 humanized T cell receptor
  • mage-a3 humanized T cell receptor

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Experimental program
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Embodiment 1

[0251] The detailed methods or steps for the transformation of humanized TCR and its cell function experimental verification are as follows:

[0252] 1. TCR Transformation

[0253] 1. Sequence Alignment

[0254] After sequence alignment, the CDR region of murine TCR was grafted onto the human TCR backbone, and the sequence of the stability site was introduced to obtain SRm1g13t (see figure 1 ).

[0255] 1.1 Align the V regions of the α and β chains of the murine TCR with the TRAV and TRBV database sequences in the human TCR library on IMGT to find the most similar sequence, such as the most similar sequence found in the present invention are TRAV18*01 and TRBV28*01 ( figure 1 -A and figure 1 -B).

[0256] 1.2 The CDR regions (CDR1, CDR2, CDR3) in the α and β chain V regions of the murine TCR were directly grafted to the corresponding framework regions of TRAV18*01 and TRBV28*01 to form the corresponding non-stability-optimized human The V region of the TCR alpha, beta ch...

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PUM

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Abstract

The invention provides a humanized transformed T cell receptor (TCR) SRm1g13t. The humanized T cell receptor has the characteristic of combining human antigen MAGE-A3:112-120(KVAELVHFL) and human leucocyte antigen (HLA) compound: pHLA(MAGE-A3), wherein the combination affinity of SRm1g13t for the pHLA(MAGE-A3) compound is at least 2 times of that of a corresponding mouse TCR SRm1 for the pHLA(MAGE-A3) compound. The invention further provides a fused molecule of TCR and a therapeutical agent. The TCR can be singly used, and can also be combined with the therapeutical agent for use.

Description

technical field [0001] The invention relates to the field of biotechnology, and more particularly relates to a humanized T cell receptor (T cell receptor, TCR) capable of recognizing human antigen pHLA (MAGE-A3). The invention also relates to the preparation and use of said receptors. Background technique [0002] At present, more and more attention is paid to T cell immunotherapy based on the expression of specific T cell receptor (TCR), which is expected to eradicate tumors. This anti-tumor effect is mediated by the transferred TCR, which can recognize the peptide-human leukocyte antigen (pHLA) complex on tumor cells, so that T cells can recognize tumor cells, and then make T cells Cell killing tumor cells. Recent studies have shown that TCR with higher affinity can make T cells exert better anti-tumor effect. Clinical trials have also shown that NY-ESO-1-specific T cells with increased affinity not only exhibit safety but also exhibit good anti-tumor efficacy. These d...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/725C12N15/12C12N5/10C12N15/867A61P35/00A61P37/00
CPCA61K35/17C07K14/7051C12N15/86C12N2740/15043
Inventor 李懿陈琳
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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