No mitogen activity anti CD3 small molecular antibody designing method

Abstract

The invention relates to an engineering method for constructing mini-antibody of non-mitogen anti-human CD3 and its usage. The antibody of CD3 with a minibody structure is constructed by CH1, CH2 region, which contains Fc receptor binding site in the structures without antibodies. The antibody can bind with the antigenic specificity of CD3 of T achroacytes' surface and can initiate immunosuppressive function and meanwhile, there is no obvious activity for promoting the mitogen. The antibody can be used for the prevention and treatment about acute rejection in organ transplantation and the treatment about type I diabetes, amyotrophic lateral sclerosis of spinal cord and other autoimmune diseases.

Description

technical field [0001] The invention relates to a design method for constructing an anti-CD3 antibody without mitogen activity. An anti-CD3 antibody with a minibody structure is constructed by deleting the CH1 and CH2 regions containing the Fc receptor binding site in the antibody structure. The obtained antibody can specifically bind to the CD3 antigen on the surface of T cells and can induce immunosuppressive function without obvious mitogenic activity. Background technique [0002] In 1986, the U.S. FDA approved the mouse-derived anti-CD3 monoclonal antibody OKT3 to enter the market for anti-rejection during organ transplantation. It is also the only CD3-targeting antibody approved for marketing so far. It has been widely used in kidney transplantation abroad, and can also be used in liver, heart, pancreas, bone marrow and other organ transplants, and has a significant effect in preventing and treating acute rejection. Studies in recent years have found that anti-CD3 an...

AI Technical Summary

Problems solved by technology

Through genetic engineering techniques, site-directed mutagenesis was performed on these sites, and a series of antibodies without mitogen activity were obtained: Humanization of point mutations at positions 234 and 235 (mutating valine Val to alanine Ala) IgG1 antibody hOKT3γ (Ala-Ala); humanized IgG2 antibody HuM291 with point mutations at positions 234 and 237 (mutating valine Val to alanine Ala); carrying out point mutations at position 297 (asparagine The amide Asn is mutated to alanine Ala), and the IgG1 antibody YTH12.5 (also known as ChAglyCD3), which reduces its glycosylation level and causes the loss of Fc receptor binding activity, has entered clinical trials, with significant curative effects and no detection Significant release of cytokines, significantly reduced toxic side effects

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