Recombinant BCG vaccine based on human MUC1 repetitive sequence and GM-CSF fusion expression

Abstract

The invention discloses a recombinant BCG vaccine based on human MUC1 repetitive sequence and GM-CSF fusion expression. Firstly, MUC1 repetitive sequence multimers and fusion genes connected with GM-CSF genes by connecting DNA are constructed, a signal peptide sequence and a Kozak sequence are further connected, and an expression vector is constructed; and the constructed fusion genes are transfected to BCG vaccines, and applied to the preparation of anti-tumor vaccine or anti-tumor medicament by using MUC1 as a target spot. The recombinant BCG vaccine realizes effective combination of antibody, adjuvant and vaccine vector so that the immunogenic property of the MUC1 tumor vaccine achieves more effective and durable effect; and simultaneously the recombinant BCG vaccine is safe, has no toxic and side effects, and can induce specific T cell immune response and durable secretion expression of the human MUC1 repetitive sequence and GM-CSF fusion protein.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, and relates to the preparation of anti-tumor vaccines, in particular to a recombinant BCG vaccine based on the fusion expression of human MUC1 repeat sequence and GM-CSF, and its preparation method and application. Background technique [0002] 1. Research on MUC1 molecules and MUC1 tumor vaccines [0003] 1.1 Molecular biology of MUC1 [0004] Mucinl mucin (MUC1), also known as polymorphic epithelial mucin (polymorphic epithelialmucin, PEM), DF3 and so on. MUC1 is a highly glycosylated type I transmembrane protein. Under normal circumstances, it is mainly expressed on the glandular surface of epithelial cells in various tissues and organs, with apical expression and polar distribution; MUC1 is abnormally expressed on the surface of cancer cells. A non-polar distribution. [0005] The MUC1 gene is located at band 21 of the long arm of chromosome 1 and consists of 7 exons with a length rang...

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Problems solved by technology

[0031] Chung et al. used BCG as an expression carrier of foreign genes for anti-tumor research, immunized hu-PBL-SCID mice with full-length MUC1 and human interleukin 2 (IL-2) recombinant BCG vaccine, and vaccinated once every 2 weeks for a total of Three times, it was found that it can inhibit the growth of breast cancer, but the immune response and protection it induces are still insufficient, which may be related to factors such as the full-length sequence of MUC1 affecting its immune effect

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