Homodimeric bispecific antibodies against cd19 and cd3, and preparation methods and uses thereof

Abstract

Provided is a tetravalent, homodimer type bispecific antibody molecule that simultaneously targets immune effector cell antigen CD3 and tumor-associated antigen CD19, the bispecific antibody molecule sequentially comprises a first and a The second single-chain Fv and the Fc fragment; wherein the first single-chain Fv can specifically bind to CD19, the second single-chain Fv can specifically bind to CD3, and the first and second single-chain Fv are connected by a linking peptide, and the second single-chain Fv is able to specifically bind to CD3 The single chain Fv is linked directly or via a linking peptide to the Fc fragment; the Fc fragment does not have effector functions such as CDC, ADCC and ADCP. The bispecific antibody can significantly inhibit or kill tumor cells, and has controlled toxic side effects that may be caused by overactivation of effector cells; in addition, this bispecific antibody is a homodimer type, and there is no heavy chain and For the problem of light chain mismatch, the purification steps are simple and efficient, the expression amount is high, and its physicochemical and in vivo stability are significantly improved.

Description

[0001] Related applications [0002] This application claims the priority of Chinese patent application CN 201811294887.4 filed on November 1, 2018. The contents of the above-referenced priority applications are incorporated herein by reference in their entirety. technical field [0003] The present invention relates to the field of immunology, more particularly, to an anti-CD3 bispecific antibody that mediates T cell killing, and uses of such antibodies, especially in the treatment of cancer, autoimmunity, inflammatory diseases and immune suppression Different uses. Background technique [0004] The body maintains homeostasis by eliminating foreign bodies through innate immunity and adaptive immunity, while adaptive immunity performs its immune function through lymphocyte B cells and T cells. One of the roles of B lymphocytes is to directly kill target cells through antibody-dependent cell-mediated cytotoxicity (ADCC). Many membrane molecules on the surface of B cells, ...

AI Technical Summary

Problems solved by technology

This systemic activation of T cells will be accompanied by a large release of cytokines, leading to serious adverse reactions during therapeutic application

Images