TCR knockout T cell receptor gene-modified T cell targeting MAGE-A3, preparation method and application thereof

Abstract

The invention provides a method for preparing TCR knockout T cell receptor gene-modified T cells targeting MAGE-A3, which comprises the following steps: by knocking out the TCR gene on T lymphocytes and preparing T cell receptors targeting MAGE-A3, and the TCR knockout T cell receptor gene-modified T cell targeting MAGE-A3 is obtained. The TCR knockout cell receptor gene-modified T cell targetingMAGE-A3 T can effectively prevent the mismatch of endogenous and exogenous TCR alpha-chain and beta-chain existing in T cells, autoimmune responses are avoided, and efficient and specific killing performance of MAGE-A3 positive tumor cells can be kept. The method also provides an application of TCR knockout T cell receptor gene-modified T cells targeting MAGE-A3.

Description

technical field [0001] The invention relates to the field of medical biology, in particular to a TCR knockout T cell receptor gene-modified T cell targeting MAGE-A3, a preparation method and application thereof. Background technique [0002] Malignant tumors are the most serious diseases that endanger human health. Every year, about 3 million people in China are diagnosed with new tumors, and 2 million people die of cancer. Human melanoma antigen-A3 (melanoma antigen-A3, MAGE-A3) is a member of the melanoma-associated antigen family. MAGE-A3 is always associated with tumors, and is mostly expressed in malignant tumor tissues mainly melanoma, and can be highly expressed in tumors of various tissue types, such as lung cancer, breast cancer, cervical cancer, gastric cancer, node- Rectal cancer, hepatocellular carcinoma, etc., but not in normal cells. Therefore, MAGE-A3 is one of the ideal target antigens for tumor-specific immunotherapy and diagnosis. [0003] In recent year...

AI Technical Summary

Problems solved by technology

However, studies have shown that there is a mismatch between the TCR transduced by TCR-T technology and the endogenous TCR subunits (such as α chain and β chain) of T cells, resulting in the target recognition ability of the mismatched TCR. Autoimmune response caused by loss or recognition of self-antigen or major histocompatibility complex (MHC)

At the same time, it is still a huge challenge to obtain TCR genes with high specificity and high affinity for tumor antigens and the correct pairing of TCR subunits

At present, there is no preparation and research related to the T cell receptor targeting MAGE-A3

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