Boosting therapeutic potency of antibodies by taming Fc domain functions

Autor: Tae Hyun Kang, Sang Taek Jung
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Experimental and Molecular Medicine, Vol 51, Iss 11, Pp 1-9 (2019)
Experimental & Molecular Medicine
ISSN: 2092-6413
1226-3613
Popis: Monoclonal antibodies (mAbs) are one of the most widely used drug platforms for infectious diseases or cancer therapeutics because they selectively target pathogens, infectious cells, cancerous cells, and even immune cells. In this way, they mediate the elimination of target molecules and cells with fewer side effects than other therapeutic modalities. In particular, cancer therapeutic mAbs can recognize cell-surface proteins on target cells and then kill the targeted cells by multiple mechanisms that are dependent upon a fragment crystallizable (Fc) domain interacting with effector Fc gamma receptors, including antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated phagocytosis. Extensive engineering efforts have been made toward tuning Fc functions by either reinforcing (e.g. for targeted therapy) or disabling (e.g. for immune checkpoint blockade therapy) effector functions and prolonging the serum half-lives of antibodies, as necessary. In this report, we review Fc engineering efforts to improve therapeutic potency, and propose future antibody engineering directions that can fulfill unmet medical needs.
Monoclonal antibodies: Engineering immunity Fine-tuning the function of monoclonal antibodies (mAbs) holds promise for developing new therapeutic agents. Antibodies bind to pathogens or cancer cells, flagging them with Fc (fragment crystallizable) domain for destruction by the immune system. mAbs attached only to specific target cells enable lower side effect than other conventional drugs. Sang Taek Jung at Korea University and Tae Hyun Kang at Kookmin University, both in Seoul, reviewed recent developments in engineering therapeutic potency of mAbs. They report that mAbs can be engineered to activate effective immune cell types to treat a particular disease. Engineering can also increase mAbs’ persistence in the blood, enabling less frequent administration. Antibodies engineered to bind to two different antigens at once can also improve therapeutic efficacy. Applying these techniques could help developing new treatments against cancer, and infectious and autoimmune diseases.
Databáze: OpenAIRE
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