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T cell receptors for recognizing human hepatitis B virus core antigens

A hepatitis B virus and cell receptor technology, applied in the direction of virus/bacteriophage, genetically modified cells, receptors/cell surface antigens/cell surface determinants, etc., can solve the problems of toxic side effects or drug resistance, high cost, etc. , to achieve the effect of treating hepatitis and good affinity

Active Publication Date: 2020-08-28
深圳市因诺转化医学研究院 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Long-term treatment with these drugs is not only expensive, but also has toxic side effects or drug resistance

Method used

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  • T cell receptors for recognizing human hepatitis B virus core antigens
  • T cell receptors for recognizing human hepatitis B virus core antigens
  • T cell receptors for recognizing human hepatitis B virus core antigens

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: HLA-A2-HBV-C 18-27 Cloning and sequencing of specific T cells

[0052] Peripheral blood mononuclear cells (PBMC) derived from HLA-A2 genotype and HBV-positive patients were stimulated in vitro by chemically synthesized short peptide FLPSDFFPSI (Sangon Bioengineering (Shanghai) Co., Ltd.). After 2 rounds of polypeptide stimulation, polyclonal T cells (1×10 5 ) and 1×10 5 T2 cells (control cells) loaded with FLPSDFFPSI short peptide (target cells) or non-target short peptides were co-cultured overnight at 37°C. The next day, the release of cytokine IFN-r in the culture supernatant was detected. Positive polyclonal T cells (target cell OD 450 - control cell OD 450 >1.0) for limiting dilution cloning, and ELISA to detect the reactivity of T cells and target cells in each well after limiting dilution after 14 days. Pick positive monoclonal T cells for rapid expansion. After 14 days of rapid amplification, with HLA-A2-HBV-C 18-27 Pentamer staining (Proimmun...

Embodiment 2

[0074] Example 2: Preparation of HLA-A2-HBV-C 18-27 specific TCR-T cells

[0075] The target TCR was cloned into the retroviral vector pMSGV1 (addgene) to construct the pMSGV1-TCR vector. The virus packaging cell line 293GP cells were transfected with pMSGV1-TCR and pVSV-G plasmids to prepare retrovirus and use the virus supernatant to transduce T cells.

[0076] The transfection operation was as follows: 293GP cells were seeded into 6-well plates (6×10 5 On the first day, pMSGV1-TCR and pVSV-G plasmids were transfected into 293GP cells (2 μg pMSGV1-TCR and 1.4 μg pVSV-G / well), and on the same day, PBMCs from healthy people were activated using anti-human CD3 antibody (OKT3) ; On the 3rd day, collect the culture fluid containing the virus supernatant, and add fresh culture fluid (DMEM containing 10% fetal bovine serum) to the 293GP cells; use the collected virus supernatant to centrifugally transfect activated T cells; On the 4th day, the activated T cells were transfected ...

Embodiment 3

[0077] Example 3: HLA-A2-HBV-C 18-27 In vitro functional verification of specific TCR-T

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PUM

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Abstract

The invention discloses a T cell receptor (TCR) for recognizing a human hepatitis B virus core antigen, and relates to the technical field of cellular immunotherapy. The TCR has the characteristic ofcombination with an HLA-A2-HBV-C18-27 antigen complex, and the TCR comprises a TCR alpha-chain variable region and / or a TCR beta-chain variable region. The invention also provides nucleic acid molecules which comprise nucleotide sequences for encoding the TCR or complementary sequence of the nucleotide sequences, and the invention provides a carrier which comprises the nucleic acid molecules, cells for transducing the nucleic acid molecules or the carrier, a pharmaceutical composition which contains the TCR, the nucleic acid molecules, the carrier or the cells as active ingredients and application of the TCR, the nucleic acid molecules, the carrier, the cells and the pharmaceutical composition. The TCR for recognizing the human hepatitis B virus core antigen has the properties of specificrecognition of the human hepatitis B virus core antigen and good affinity.

Description

technical field [0001] The present invention relates to the technical field of cellular immunotherapy, in particular to a TCR capable of specifically recognizing and binding to the core antigen of human hepatitis B virus, and a nucleic acid molecule comprising a nucleotide sequence encoding the TCR or its complementary sequence, as well as a nucleic acid molecule comprising the TCR A carrier of a nucleic acid molecule, and a cell that transduces the nucleic acid molecule or the vector, and a pharmaceutical composition comprising the TCR, the nucleic acid molecule, the vector, or the cell as an active ingredient, and the TCR, the nucleic acid molecule, the vector, the cell , The purposes of pharmaceutical composition. Background technique [0002] Hepatitis B is an infectious inflammation of the liver caused by hepatitis B virus (Hepatitis B Virus, HBV), and is the most serious type of viral hepatitis. HBV is a partially circular double-stranded DNA virus with a total genome...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/725C12N15/12C12N15/867C12N5/10A61K35/17A61P35/00A61P31/20A61P1/16
CPCC07K14/7051C12N15/86C12N5/0636A61K35/17A61P35/00A61P31/20A61P1/16C12N2740/10043C12N2800/107C12N2510/00
Inventor 王明军马意朋区家裕林通
Owner 深圳市因诺转化医学研究院
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