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Structural biology of antibody recognition of carbohydrate epitopes and potential uses for targeted cancer immunotherapies.

Abstract
Monoclonal antibodies represent the most successful class of biopharmaceuticals for the treatment of cancer. Mechanisms of action of therapeutic antibodies are very diverse and reflect their ability to engage in antibody-dependent effector mechanisms, internalize to deliver cytotoxic payloads, and display direct effects on cells by lysis or by modulating the biological pathways of their target antigens. Importantly, one of the universal changes in cancer is glycosylation and carbohydrate-binding antibodies can be produced to selectively recognize tumor cells over normal tissues. A promising group of cell surface antibody targets consists of carbohydrates presented as glycolipids or glycoproteins. In this review, we outline the basic principles of antibody-based targeting of carbohydrate antigens in cancer. We also present a detailed structural view of antibody recognition and the conformational properties of a series of related tissue-blood group (Lewis) carbohydrates that are being pursued as potential targets of cancer immunotherapy.
AuthorsTamir Dingjan, Ian Spendlove, Lindy G Durrant, Andrew M Scott, Elizabeth Yuriev, Paul A Ramsland
JournalMolecular immunology (Mol Immunol) Vol. 67 Issue 2 Pt A Pg. 75-88 (Oct 2015) ISSN: 1872-9142 [Electronic] England
PMID25757815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Antibodies
  • Carbohydrates
  • Epitopes
  • Lewis Blood Group Antigens
  • Lewis Y antigen
Topics
  • Antibodies (immunology, metabolism, therapeutic use)
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Carbohydrates (chemistry, immunology)
  • Epitopes (chemistry, immunology, metabolism)
  • Humans
  • Immunotherapy (methods)
  • Lewis Blood Group Antigens (chemistry, immunology, metabolism)
  • Molecular Sequence Data
  • Neoplasms (immunology, therapy)

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