Monoclonal antibody specifically binding to human CD47 and application thereof

Abstract

The invention provides a monoclonal antibody specifically binding to human CD47 or a fragment thereof, which can bind to CD47 on the surface of a cell and block binding of SIRP alpha to CD47 on the surface of the cell. The affinity KD value on the recombinant human CD47 is between 1 * 10 <-10 > and 8 * 10 <-8 >, and the tumor inhibition activity and the adverse reaction activity can be balanced. In the aspect of tumor inhibition activity, the antibody can inhibit tumor growth in a CD47 / SIRP alpha double-transgenic mouse tumor-bearing hCD47-MC38 subcutaneous transplanted tumor model, and can enhance in-vivo cell phagocytosis and prolong the lifetime of a mouse in a mouse leukemia model of transplanted human acute B lymphocytic leukemia; in the aspect of adverse reaction activity, the antibody does not have or only has reduced erythrocyte agglutination activity, and does not have a significant effect or only has an over-sexual effect on erythrocytes, platelets and hemoglobin.

Description

[0001] priority information [0002] This application claims priority to and the benefit of the patent application No. 202011253602.X filed with the State Intellectual Property Office of China on November 11, 2020, which is hereby incorporated by reference in its entirety. technical field [0003] The invention belongs to the field of antibody engineering, and in particular relates to a monoclonal antibody that specifically binds to human CD47, its fragment, preparation method and use, in particular to a monoclonal antibody that can block the binding of SIRPα and CD47 and has low erythrocyte toxicity The anti-human CD47 monoclonal antibody and its application. Background technique [0004] CD47, also known as integrin-associated protein (IAP), ovarian cancer marker (OV-3), is a member of the immunoglobulin superfamily and is a 5-time transmembrane glycoprotein of about 50KD, containing three domains : The extracellular amino terminus is an IgV-like domain containing 5 glyco...

AI Technical Summary

Problems solved by technology

[0007] Due to the large expression of CD47 on the surface of red blood cells, platelets and other cells, the clinical application of this target antibody faces two problems: 1. The toxicity of red blood cells and platelets can be restored by adjusting the dosage regimen and the body's own compensatory function. Candidate molecules with too high affinity still face greater risks; 2. Due to the excessive consumption of antibodies in the body caused by the precipitation of a large number of antigens, the blood concentration of the drug is low, and it is difficult to achieve an effective blood concentration at the tumor site, so that the clinical dosage is relatively low. high

Therefore, a specific antibody against human CD47 with good antitumor efficacy and low toxicity to red blood cells and platelets remains to be studied.

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