Antibody conjugate with boron ester unit polymers and method for fabricating antibody conjugate

Abstract

The invention belongs to the technical field of medicines, and particularly discloses an antibody conjugate with boron ester unit polymers and a method for fabricating the antibody conjugate. The method includes carrying out reaction on 2-(hydroxymethyl) phenylboronic acid cyclic monoester units on polymer carriers and o-glycol groups of sugar chains on crystalizable fragments at Y-shaped lower ends of antibodies; forming five-membered boron ester rings at the room temperature under neutral pH (potential of hydrogen) conditions; conjugating polymers with the2-(hydroxymethyl) phenylboronic acidcyclic monoester units, derivatives of the polymers and the antibodies. The antibody conjugate and the method have the advantages that the integrity of the antibodies and recognition functions of fragments of antigen binding of Y-shaped upper arms of the antibodies can be reserved by the antibody conjugate to the greatest extent; the appropriate polymers with the 2-(hydroxymethyl) phenylboronic acid cyclic monoester units and the appropriate derivatives of the polymers are selected to be bound with different medicines or medicine carriers and are further conjugated with the different antibodies, and accordingly the purpose of pertinently treating different types of cancer can be achieved; the antibody conjugate has a broad development prospect in clinical application in consideration of the excellent biocompatibility, excellent tumor targeting effects and the universality to the different types of cancer.

Description

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

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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