PMID: 19920917Nov 19, 2009Paper

Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC.

Drug Design, Development and Therapy
Akito NatsumeMitsuo Satoh

Abstract

As platforms for therapeutic agents, monoclonal antibodies (MAbs) have already been approved, and several MAbs have demonstrated clinical effectiveness in a variety of malignancies. However, several issues have also been emerging in antibody therapy, such as high cost and insufficient drug action. Recently, to improve MAb activity in humans, effector functions have been subjects of focus, especially antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Extensive efforts have been made to enhance these effector functions of MAbs, and successful approaches have been reported by us and others, wherein the binding activity of MAbs to FcgammaRIIIa or C1q is increased by introducing amino acid mutations into heavy chain constant regions or through glyco-modification of Fc-linked oligosaccharides. In addition, one of the next approaches to optimizing therapeutic antibodies would be to combine multiple enhancing modifications into a single antibody platform to overcome the diverse mechanisms of clinical resistance of tumor cells. For this aim, we have recently developed a successful combination composed of ADCC-enhancing modification by the fucose depletion from Fc-linked oligosaccharides and...Continue Reading

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Citations

Oct 5, 2013·Lancet Neurology·Jiwon Oh, Peter A Calabresi
Aug 3, 2017·International Journal of Molecular Sciences·Rosa MolfettaRossella Paolini

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