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Specific T cell receptor targeting cytomegalovirus antigen and application thereof

A technology of cytomegalovirus and cell receptors, which is applied in the field of specific T cell receptors targeting cytomegalovirus antigens, can solve the problems of missing TCR pairing information and complicated screening procedures, and achieve the effect of simple and easy-to-operate preparation methods

Active Publication Date: 2021-07-16
SHENZHEN HUADA GENE INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its complex screening process and lack of TCR pairing information have become obstacles to its wide application

Method used

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  • Specific T cell receptor targeting cytomegalovirus antigen and application thereof
  • Specific T cell receptor targeting cytomegalovirus antigen and application thereof
  • Specific T cell receptor targeting cytomegalovirus antigen and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0060] In this case, antigen-specific cytotoxic T lymphocytes were induced and expanded in vitro based on HLA-A*0201-typed antigen CMV pp65 antigen NLV epitope polypeptide NLVPMVATV, and positive T cells were sorted by single-cell sequencing and MHC tetramer According to the TCR pairing information, TCR was screened according to the clone sequence frequency, TCR-T was constructed, functional verification was carried out in vitro, and the function of TCR-T was evaluated to finally determine the specific T cell receptor in this case. The details are as follows:

[0061] 1. Induction and functional detection of CMV pp65 NLV-specific cytotoxic T lymphocytes

[0062] 1.1 Induction of CMV pp65 NLV-specific cytotoxic T lymphocytes

[0063] 50 mL of peripheral blood from healthy people with HLA-A*0201 typing was collected, and peripheral blood mononuclear cells (PBMC) were obtained by Ficoll density gradient centrifugation. From the isolated PBMC, CD14 was sorted using anti-CD14 ant...

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Abstract

The invention discloses a specific T cell receptor targeting a cytomegalovirus antigen and application of the specific T cell receptor. The specific T cell receptor targeting the cytomegalovirus antigen can be specifically combined with cytomegalovirus phosphoprotein pp65 in a targeting manner, an alpha chain and a beta chain of the specific T cell receptor respectively have three complementary determining regions, and the three complementary determining regions of the alpha chain are sequences shown as SEQ ID No.4, SEQ ID No.5 and SEQ ID No.2 in sequence; and the three complementary determining regions of the beta chain are sequences shown as SEQ ID No.6, 7 and 3 in sequence. The specific T cell receptor disclosed by the invention can be specifically combined with the antigen epitope polypeptide of cytomegalovirus phosphoprotein pp65 in a targeting manner, and a new scheme is provided for TCR-T treatment of cytomegalovirus related diseases; in addition, the preparation method of the specific T cell receptor is simple and easy to operate, and a foundation is laid for popularization and application of TCR-T treatment based on the specific T cell receptor.

Description

technical field [0001] The present application relates to the field of cytomegalovirus, in particular to a specific T cell receptor targeting cytomegalovirus antigen and its application. Background technique [0002] Cytomegalovirus (CMV) is a member of the herpes virus family. Symptoms after CMV infection vary widely, ranging from no symptoms to general discomfort and fever, and severe symptoms such as blindness, brain and internal organ damage in immunocompromised persons and fetuses. The virus can be spread through sexual or non-sexual bodily fluids. At the same time, CMV infection is also common in organ transplantation and bone marrow transplantation, and is an important factor causing disease and death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, current antiviral drugs, such as acyclovir, valganciclovir, and ganciclovir, often cause severe side effects, and with the development of drug-resistant virus strains, the treatment of such ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/725C12N15/12C12N15/867C12N5/10A61K38/17A61K35/17A61P31/22
CPCC07K14/7051C12N15/86C12N5/0636A61K35/17A61P31/22C12N2740/15043C12N2800/107C12N2510/00A61K38/00
Inventor 徐曲苗朱琳楠王飞赵正琦林玉琪李子怡顾颖侯勇
Owner SHENZHEN HUADA GENE INST