Bispecific antibody against IGF1R and CD3, minicircle DNA containing bispecific antibody expression cassette, and application thereof

Abstract

The invention provides a bispecific antibody, and a preparation method and application thereof. The bispecific antibody has a first antigen binding domain specifically binding to human CD3 and a second antigen binding domain specifically binding to an IGF1R antigen, and can specifically recognize and bind to the IGF1R antigen and IGF1R-overexpressed tumor cells, including cells of liver cancers and other IGF1R-positive tumors; the bispecific antibody can bind to T-cell receptors and mediate T-cell cytotoxicity to clear IGF1R infections, and has great application value in diagnosis, treatment,prevention and detection of IGF1R-related diseases. The invention also provides a minicircle DNA having a nucleotide sequence encoding the bispecific antibody. The bispecific antibody and the minicircle DNA provided by the invention can be used for preparing antibody drug compositions or preparing diagnostic reagents for IGF1R-positive tumor cells.

Description

technical field [0001] The invention relates to the fields of biomedicine and diagnosis and treatment, in particular to an anti-IGF1R and CD3 specific dual-targeting antibody, a microcircle DNA containing the expression cassette of the dual-targeting antibody, and applications. Background technique [0002] Insulin-like growth factors (IGFs) system is an attractive target for tumor therapy. It was discovered by Saman and Daughaday in 1957. It is named for its high homology with insulin and its action similar to insulin. IGFs consist of two ligands (IGF1 and IGF2), two receptors (IGF1R, IGF2R) and six high-affinity binding proteins (IGFBPs). IGF1R is a transmembrane tyrosine protein kinase receptor, which exists in the form of a tetramer composed of the α subunit of the extracellular segment and the β subunit of the transmembrane region, and stimulates its own β subunit by disulfide bond binding to IGF ligands. Phosphorylation of phosphoinositide 3-kinase (PI3K)-protein kina...

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Problems solved by technology

[0009] (5) Dalotuzumab antibody, developed by Merck & Co., is a humanized antibody with low immunogenicity, but it can only bind to IGF1R antigen and IGF1R-positive cells, and cannot bind to T cells and cannot mediate T cell killing ; Can only be targeted to kill IGF1R antigen-positive tumor cells by ADCC or CDC

At present, it has progressed to clinical II trials: for a variety of advanced tumors (non-small cell lung cancer, colon cancer, ovarian cancer, etc.), the effect is unknown

[0010] (6) The robatumumab antibody, jointly developed by Merck&Co. and Schering-Plough, is a humanized antibody with low immunogenicity, but it can only bind to IGF1R antigen and IGF1R-positive cells, and cannot bind to T cells. Mediates T cell killing; can only target IGF1R antigen-positive tumor cells by ADCC or CDC

[0011] Several IGF1R antibodies currently reported can only bind to IGF1R antigen and IGF1R-positive cells, but cannot bind to T cells and cannot mediate T cell killing; they can only target and kill IGF1R antigen-positive tumor cells through ADCC, CDC or radioisotope labeling

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