Fully humanized single-domain antibody for CD16, antigen combining fragment of antibody and applications

Abstract

The invention belongs to the biotechnological field and particularly relates to a fully humanized single-domain antibody for CD16, an antigen combining fragment of the antibody and applications of theantibody and the antigen combining fragment in preparation of preparations for disease diagnosis and treatment. The invention discloses the fully humanized single-domain antibody capable of specifically combining CD16 or the antigen combining fragment of the antibody. The single-domain antibody is mainly characterized by being determined by a CDR (complementarity-determining region) specific genesequence existing in an antibody heavy chain gene variable region, and the effectively expressed antibody specifically combined with the CD16 is obtained from prokaryotic and eukaryotic cells. Different forms of genetically engineered antibodies can be modified and produced in prokaryotic and eukaryotic cells and any expression system by use of the CDR or partial or full gene of the body, and theantibody can be used for preparing preparations for clinical diagnosis or treatment of related diseases.

Description

technical field [0001] The invention belongs to the field of biotechnology, and specifically relates to fully human single-domain antibodies against CD16, antigen-binding fragments thereof, and their application in preparation of preparations for disease diagnosis and treatment. Background technique [0002] The prior art discloses that CD16 (also known as FcRγIII) is a low-affinity receptor of the Fc fragment of IgGs, which can trigger the lysis of target cells by natural killer cells (NKs) cells. Studies have shown that human NK cells contain about 15% of lymphocytes, and most NK cells have low expression of CD56 (CD56 dim ), while the expression level of CD16 was high. Human CD16 has two isoforms, CD16A and CD16B, both of which show a sequence identity of 96% in the sequence of the extracellular immunoglobulin binding region. CD16A is a transmembrane receptor expressed by macrophages, mast cells and NK cells. It co-localizes with CD3ζ and Fc-εRI-γ on NK cells. Once the ...

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Problems solved by technology

Therefore, the industry has developed an immunotherapy method that uses the activity of CD16 to treat cancer, such as bispecific molecules formed by antibodies specific to tumor surface antigens and CD16 specific antibodies on NK cells. Currently, HER2 / neu and CD16 bispecific antibody, which has stronger anti-tumor activity than HER2 antibody alone; HRS-3 / A9, a bispecific antibody that specifically binds CD16 and CD30, can bind to the surface of NK cells or monocytes The CD16 molecule enables these immune effector cells to target CD30-expressing tumor cells for killing, and the antibody can completely eliminate tumors in both Hodgkin's tumor mouse models and patients, ， However, these murine antibodies have a short half-life in humans

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