Chimeric antigen receptor and cell expressing same and preparation method and application of chimeric antigen receptor

Abstract

The invention relates to a chimeric antigen receptor, nucleic acid coding the chimeric antigen receptor, a construct containing nucleic acid, an expression vector, a transformed cell and pharmacy application of the chimeric antigen receptor, nucleic acid coding the chimeric antigen receptor, the construct containing nucleic acid, the expression vector and the transformed cell. The chimeric antigen receptor comprises at least one extracellular domain, an optional transmembrane domain and at least one intracellular signal transduction domain, wherein each extracellular domain comprises an SC-FV fragment derived from a heavy chain and a light chain of an MUC1 or PSCA specific monoclonal antibody or gene modification which is conducted on the basis of the domain and an optimal signal peptide, and each intracellular signal transduction domain comprises a immune costimulatory signal combination. According to the transformed cell, the capacity of the transformed cell for killing solid tumor cells in vitro and in vivo is significantly improved and is higher than that of a conventional chimeric antigen receptor with a structure of the second generation.

Description

technical field [0001] The invention relates to the technical field of tumor cell immunotherapy, in particular to a chimeric antigen receptor, a nucleic acid encoding it, a construct containing the nucleic acid, an expression vector and transformed cells, and their pharmaceutical use. Background technique [0002] In recent years, the incidence and mortality of lung cancer have been increasing, making it one of the most serious types of cancer worldwide. Especially in China, the incidence of lung cancer has risen rapidly in the past ten years, mainly due to the rapid increase in the number of smokers (mostly men). According to statistics, about 3,000 people die from smoking every day[1]. Lung cancer is mainly divided into two categories: small cell lung cancer (15%) and non-small cell lung cancer, of which non-small cell lung cancer can be further divided into adenocarcinoma (40%), squamous cell carcinoma (30%) and large cell carcinoma (15%). %). Different types of lung ca...

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Problems solved by technology

[0005] Based on the existing problems and deficiencies in the current treatment of lung cancer, for example: First, about 80% of lung cancer patients have entered the advanced metastatic stage when they are discovered, and cannot be surgically removed

In about 20% of cases that can be treated, recurrence often occurs in the later stage, and the five-year survival rate is very low; second, non-small cell lung cancer is less sensitive to radiotherapy and chemotherapy, and the treatment effect is not good; third, targeting at The effects of targeted drugs for lung cancer with gene mutations such as EGFR and ALK are relatively short-lived, and the tumor will acquire resistance in about a year

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