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Bispecific antibody resisting CD16A antigen and MUC1antigen

A bispecific antibody and specific technology, applied in the field of genetic engineering, can solve problems such as insufficient curative effect, achieve the effect of enhancing killing ability, overcoming insufficient curative effect, and overcoming small molecular weight

Active Publication Date: 2016-03-02
SHENZHEN BEIKE BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In view of the above technical problems, the present invention discloses a bispecific antibody against CD16A antigen and anti-MUC1 antigen. Based on the problem of insufficient curative effect in the treatment of tumors with a single recognition in the prior art, the present invention discloses a bispecific antibody capable of simultaneously combining The bispecific antibody of tumor-associated antigens and immune cell target molecules recognizes the MUC1 antigen of liver cancer cells and induces ADCC, and at the same time recognizes the CD16A antigen of immune effector cells, effectively guiding the specific killing of tumor cells by immune effector cells

Method used

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  • Bispecific antibody resisting CD16A antigen and MUC1antigen
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  • Bispecific antibody resisting CD16A antigen and MUC1antigen

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Embodiment Construction

[0039] The preferred embodiments of the present invention will be further described in detail below in conjunction with the accompanying drawings.

[0040] 1. Preparation of bispecific antibody:

[0041] (1) Bispecific antibody construction

[0042] VL of anti-CD16A antibody and VH of anti-MUC1 pass through G 4 The S sequence is connected to form the first ScFv, the VL of the anti-MUC1 antibody and the VH of the anti-CD16A through the G 4 The S sequence is connected to form the second ScFv. The two ScFvs are connected in series through a longlinker, and at the same time, they are directly connected to the CH2 and CH3 of IgG1 after the second ScFv, and the leader peptide sequence of IgG is used as the signal peptide, such as figure 1 shown. The cDNA sequence of the artificially synthesized double antibody after codon optimization. The VL amino acid sequence of the anti-CD16A antibody is shown in SEQ ID NO: 1, the VH amino acid sequence of the anti-MUC1 antibody is shown in ...

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Abstract

The invention provides a bispecific antibody resisting a CD16A antigen and an MUC1 antigen. The bispecific antibody comprises a first functional domain capable of specifically recognizing the CD16A antigen of immunologic effector cells, a second functional domain capable of specifically recognizing the MUC1 antigen of liver cancer cells and a linker linking the two functional domains. According to the technical scheme, the bispecific antibody can combine tumor-associated antigen and target molecules of immune cells, can recognize the MUC1 antigen of the liver cancer cells and induce ADCC (antibody-dependent cell-mediated cytotoxicity) and recognize the CD16A antigen of the immunologic effector cells, improves the killing capacity of NK (natural killer) cells on tumor cells, effectively guides the immunologic effector cells to perform specific killing on the tumor cells and has a stable structure and a longer half-life period.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, in particular to a bispecific antibody against CD16A antigen and anti-MUC1 antigen. Background technique [0002] CD16A (FcγRⅢA) is a transmembrane IgG Fc receptor with an extracellular region of 190AA and an intracellular region of 25AA. It belongs to the Ig superfamily and is mainly distributed in NK (natural killer, natural killer) cells, macrophages and Eosinophil surface. Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important effector function of an antibody. When an antibody binds to a target cell (such as a tumor cell), the Fc end of the antibody can pass through the Fc receptor (CD16A) Combine with NK cells and activate NK cells, which will kill target cells by releasing granzyme and perforin. CD16A mediates the ADCC function of NK cells and monocyte-macrophages, plays an important role in specific and non-specific immunity, and is a key receptor for the body t...

Claims

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Application Information

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IPC IPC(8): C07K16/46C07K16/30C07K16/28C12N15/13C12N15/85A61K39/395A61P35/00
CPCA61K39/39558C07K16/2803C07K16/303C07K16/468
Inventor 胡祥吴春风刘佳刘沐芸李陶
Owner SHENZHEN BEIKE BIOTECH
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