Anti-CD3 and anti-CD19 bispecific antibody

Abstract

The invention relates to the field of biological medicines, and specifically provides an anti-CD3 and anti-CD19 bispecific antibody, which includes a single-chain unit capable of specifically bindingto a CD3 antigen and a monovalent unit capable of specifically binding to a CD19 antigen. The single-chain unit and the monovalent unit both include a complete light chain and a complete heavy chain,and the C terminal of the light chain of the single-chain unit is connected with the N terminal of the heavy chain through a linker. According to the invention, the biological activities of the anti-CD19 antibody and the anti-CD3 antibody are completely retained; tumor cells and effector cells can be better recognized; the effector cells are targeted to the tumor cells to achieve the specific lethal effect, and the lethal ability is higher; and since the light chain and the heavy chain of the single-chain unit are bonded through the linker, mismatch between the light chain and the heavy chainin the bispecific antibody is effectively avoided, the difficulty in purification is solved, and a solid foundation is provided for amplified production of the bispecific antibody.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to an anti-CD3 and anti-CD19 bispecific antibody. Background technique [0002] With the continuous development of biological drugs, therapeutic antibodies have become the main drug of choice for patients with cancer, autoimmunity, inflammation and various other diseases. However, monoclonal antibodies have their limitations. These antibodies are directed against a single target. Many patients do not respond adequately to a single therapy, and patients may develop resistance or non-response. Cancer is different from other diseases. It is a multifactorial disease, and multiple signaling pathways are involved in the occurrence of the disease. It seems that single-target immunotherapy is not enough to destroy cancer cells. is recognized. Bispecific antibody (bispecific antibody, BiAb) is an artificial antibody containing two specific antigen-binding sites, which can specifically ...

AI Technical Summary

Problems solved by technology

[0006] At present, Blincyto is the only bispecific antibody on the market against CD3 and CD19 antigens. Blincyto uses a linker to directly connect the anti-CD19 light chain variable region, anti-CD19 heavy chain variable region, anti-CD3 heavy chain variable region, and anti-CD3 light chain variable region. The variable region does not contain the Fc fragment, so the half-life of the pharmacological molecule in the drug is relatively short. In addition, in other existing double-antibody drug molecules, even if the Fc fragment is retained in order to prolong the half-life of the drug, the modification of the Fc region makes the bismuth There is no natural monoclonal antibody stability in the body, and it is easy to produce mismatches between light and heavy chains. Therefore, it is urgent to develop a method that can not only retain the Fc fragment, prolong the half-life of the drug molecule, but also have a stable structure and avoid light and heavy chains. Anti-CD3 and anti-CD19 bispecific antibodies with mismatch between molecules

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