Novel chimeric antigen receptor targeting tumor cell surface muc1 and preparation method of muc1 chimeric antigen receptor T cell

Abstract

The present invention provides a novel chimeric antigen receptor targeting MUC1 on the surface of tumor cells and a method for preparing MUC1 chimeric antigen receptor T cells, which solves the problem of dissociation of MUC1 antibody in all current clinical trials due to its ability to recognize and fall off from cells. The N-terminus of MUC‑1 in the blood cannot effectively target tumor cells and the technical defects of targeted therapy for MUC1-positive tumors. The humanized HzMUC1 antibody in the preparation technology of this patent only recognizes MUC1 on the surface of tumor cells, and does not recognize the N-terminus of MUC-1 free in the blood, which can more effectively target and treat MUC1-positive tumors. After the new MUC1.28.BB.z CAR‑T cells are co-cultured with MUC1-positive tumor cells, the killing effect on target cells is significant, which will lay the foundation for enhancing the tumor immunotherapy effect of anti-MUC1 CAR‑T cells, and is effective against MUC1-positive solid tumors. Immunotherapy has practical guiding significance.

Description

technical field [0001] The invention specifically relates to the field of biotechnology, and specifically relates to a novel chimeric antigen receptor targeting tumor cell surface MUC1 and a preparation method of MUC1 chimeric antigen receptor T cells. Background technique [0002] Mucin 1 (MUC1) is a high-molecular-weight cell surface transmembrane glycoprotein. , MUC1 were overexpressed. MUC1 protein has been proven to play a key role in promoting tumor cell growth, enhancing stem cell characteristics, drug resistance, etc., so it is one of the important targets for tumor biotherapy. [0003] The GSVVV motif in the sea urchin spermatin, enterokinase and agrin (SEA) domains of the MUC1 protein is cleaved to form two subunits, MUC1-N (α subunit) and MUC1-C (β subunit). The N-terminus of MUCl consists of signal peptide, variable tandem repeat region (VNTR) and SEA domain. The VNTR region contains 20 to 125 tandem repeats of 20 amino acids, where serine and threonine are p...

AI Technical Summary

Problems solved by technology

[0008] These clinical trials have clearly demonstrated the role of CAR-T cells in the effective treatment of malignant tumors. So far, CAR-T cell immunotherapy has achieved encouraging results in the treatment of hematological tumors such as B-cell malignancies, but it is not effective for patients with solid tumors. poor remission rate

[0009] Some of the major challenges facing CAR-T cell immunotherapy in solid tumors include: (1) lack of tumor-unique target antigens, (2) only a limited number of CAR-T cells infiltrating into the tumor stroma, (3) tumor heterogeneity and the absence of related antigens, (4) the inhibitory effect of the tumor microenvironment on immune cells, etc.

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