FGFR4-and-DR5-targeting chimeric antigen receptor T cell as well as preparation method and application thereof

Abstract

The invention provides a FGFR4-and-DR5-targeting chimeric antigen receptor T cell as well as a preparation method and application thereof. The chimeric antigen receptor T cell comprises a FGFR4-targeting himeric antigen receptor CAR-FGFR4 and a DR5-targeting chimeric antigen receptor CAR-DR5; the CAR-FGFR4 comprises a FGFR4-targeting single-chain antibody, an extracellular hinge region, a transmembrane region and an intracellular signal region which are sequentially connected from an amino terminal to a carboxyl terminal; the CAR-DR5 comprises a DR5-targeteing single-chain antibody, an extracellular hinge region, a transmembrane region and an intracellular signal region which are sequentially connected from an amino terminal to a carboxyl terminal; and the FGFR4-targeting single-chain antibody comprises at least one kind of the following components of (a) a single-chain antibody heavy chain VH as shown in SEQ ID NO: 1 and a single-chain antibody light chain VL as shown in SEQ ID NO: 2; and (b) a single-chain antibody heavy chain VH as shown in SEQ ID NO: 3 and a single-chain antibody light chain VL as shown in SEQ ID NO: 4.

Description

technical field [0001] The invention relates to the field of medical biology, in particular to a chimeric antigen receptor T cell targeting FGFR4 and DR5 and its preparation method and application. Background technique [0002] Primary liver cancer is one of the most common malignant tumors and the second leading cause of cancer death worldwide, which has seriously threatened people's health and life. The common clinical treatment methods for liver cancer mainly include surgical resection, liver transplantation, chemotherapy and radiation therapy. However, since the early symptoms of liver cancer are not obvious and thus difficult to be detected, most patients are already in the middle and late stages when they are diagnosed, and lose the chance of surgical treatment and liver transplantation. In actual treatment, about 90% of patients with liver cancer need to receive drug treatment. Although the existing commonly used antineoplastic drugs can effectively prolong the surv...

AI Technical Summary

Problems solved by technology

FGFR4 selective inhibitors are basically covalent reversible or irreversible inhibitors based on Cys552. Once this site is mutated, it is likely to lead to drug resistance.

At present, there is no preparation and research of chimeric antigen receptor T cells targeting FGFR4 and DR5 at the same time

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