A kind of antibody conjugate containing boron ester unit polymer and its construction method

Abstract

The invention belongs to the technical field of medicine, and specifically relates to an antibody conjugate containing a boron ester unit polymer and a construction method thereof. In the present invention, the cyclic monoester unit of 2-(hydroxymethyl)phenylboronic acid on the polymer carrier reacts with the adjacent diol group of the sugar chain on the crystallizable segment at the Y-shaped lower end of the antibody to form a five The boroester ring is used to couple the polymer and its derivatives with 2-(hydroxymethyl)phenylboronic acid cyclic monoester unit to the antibody. The antibody conjugate obtained by the present invention can retain the integrity of the antibody and the recognition function of the Y-shaped upper arm antigen-binding fragment of the antibody to the greatest extent; Combining polymers and their derivatives with different drugs or drug carriers, and then coupling with different antibodies, can achieve the purpose of targeted treatment of different types of cancer. In view of the excellent biocompatibility and tumor targeting effect, as well as the universality for different types of cancer, this antibody conjugate has broad development prospects in clinical application.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a class of antibody conjugates and a preparation method thereof. Background technique [0002] Traditional chemotherapy has poor selectivity, and severe side effects can lead to death of patients. Therefore, targeted therapy is one of the ways to achieve this goal while reducing the systemic toxicity of chemotherapy drugs and enhancing the effect on tumors. Compared with normal tissue cells, different antigens are overexpressed on the surface of cancer cells, and the use of antibodies corresponding to certain antigens to specifically direct therapeutic agents to cancer cells is a research direction in the field of targeted therapy. The part on the antibody that recognizes the antigen is the antigen-binding fragment (Fab, fragment of antigen binding). When the antibody is oriented correctly, it can bind to the antigen. Otherwise, the antibody-antigen binding rate wi...

AI Technical Summary

Problems solved by technology

The part on the antibody that recognizes the antigen is the antigen-binding fragment (Fab, fragment of antigen binding). When the antibody is oriented correctly, it can bind to the antigen. Otherwise, the antibody-antigen binding rate will be significantly reduced, and effective targeted therapy cannot be achieved. An important reason why targeted therapies have not become routine in clinical practice

Combining chemotherapy drugs with antibodies to form antibody-drug conjugates (Antibody-Drug Conjugates, ADCs) can solve the problem of antibody orientation to a certain extent, but these conjugation techniques still have the following problems: (1) The preparation process is cumbersome, and the antibody There is a possibility of denaturation during the preparation process, resulting in loss of targeting function; (2) In the obtained antibody-drug conjugates, the drug / antibody ratio is not uniform, and the conjugates with unconjugated or less drugs are less effective. Low, it will compete with effectively coupled products to bind to cancer cell surface antigens, reducing the therapeutic effect; (3) It is impossible to flexibly adjust the types of antibodies or drugs according to different types of cancer cells, and the universality is poor

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