TCR knockout T cell receptor gene-modified T cell targeting TIPE3, preparation method and application thereof

Abstract

The invention provides a method for preparing TCR knockout T cell receptor gene-modified T cells targeting TIPE3, which comprises the following steps: by knocking out the TCR gene on T lymphocytes andpreparing T cell receptors targeting TIPE3, and the TCR knockout T cell receptor gene-modified T cell targeting TIPE3 is obtained. The TCR knockout T cell receptor gene-modified T cell targeting TIPE3 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 performanceof TIPE3 positive tumor cells can be kept. The method also provides an application of TCR knockout T cell receptor gene-modified T cells targeting TIPE3.

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 TIPE3, a preparation method and application thereof. Background technique [0002] Tumor necrosis factor α-inducible protein 8-like 3 (TNFAIP8L3, TIPE3) is a member of the TNFAIP3 family, which acts as a lipid second messenger transport protein to promote carcinogenesis, and acts as a feedback enhancer to regulate carcinogenesis and phospholipid pathways. TIPE3mRNA can be detected in many tissues, but TIPE3 protein is rarely expressed in normal tissues, but its expression is significantly increased in cancerous tissues. Therefore, TIPE3 is a very suitable tumor-specific target for cellular immunotherapy. [0003] In recent years, immune cell therapy has become a treatment method with great prospects in the treatment of malignant tumors after surgery, radiotherapy, and chemotherapy. T cell receptor (T cell receptor, TCR...

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 research and research on targeting the T cell receptor of TIPE3 while avoiding the mismatch between TCR transduced by TCR-T technology and T cell endogenous TCR subunits

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