Antigen-binding molecule comprising altered antibody variable region

Abstract

An antigen-binding molecule capable of binding to multiple different antigens (e.g., CD3 on T cells, and CD137 on T cells, NK cells, DC cells, and / or the like), but does not nonspecifically crosslink two or more immune cells such as T cells is provided. Such multispecific antigen-binding molecule is capable of modulating and / or activating an immune response while circumventing the cross-linking between different cells (e.g., different T cells) resulting from the binding of a conventional multispecific antigen-binding molecule to antigens expressed on the different cells, which is considered to be responsible for adverse reactions when the multispecific antigen-binding molecule is used as a drug.

Description

technical field [0001] The invention provides antigen-binding molecules capable of modulating and / or activating an immune response; pharmaceutical compositions comprising any of said antigen-binding molecules; and methods of producing said antigen-binding molecules. Background technique [0002] Antibodies have high stability in plasma and produce few adverse reactions, thus attracting attention as drugs (Nat. Biotechnol. (2005) 23, 1073-1078 (NPL 1) and Eur J Pharm Biopharm. (2005) 59 (3), 389-396 (NPL 2)). Antibodies not only have antigen-binding effects and agonist or antagonist effects, but also induce effector cell-mediated cytotoxic activity (also known as effector function), such as ADCC (antibody-dependent cellular cytotoxicity), ADCP (antibody-dependent cellular phagocytosis) effect) or CDC (complement-dependent cytotoxicity). In particular, antibodies of the IgGl subclass exhibit effector functions against cancer cells. Accordingly, a large number of antibody dr...

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Problems solved by technology

However, the side effects of this CD137 agonist antibody are problematic both clinically and non-clinically due to its non-specific liver toxicity, and the development of agents has not progressed (Dubrot, Cancer Immunol. Immunother., 2010, 28, 512-22( NPL 22))

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