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

Tamir Dingjan, Ian Spendlove, Lindy G Durrant, Andrew M Scott, Elizabeth Yuriev, Paul A Ramsland

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)75-88
Number of pages14
JournalMolecular Immunology
Volume67
Issue number2
DOIs
Publication statusPublished - 2015

Keywords

  • Antibody tumor targeting
  • Blood group carbohydrates
  • Cancer immunotherapy
  • Carbohydrate conformations
  • Carbohydrate recognition
  • Protein-carbohydrate interactions

Cite this

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title = "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.",
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Structural biology of antibody recognition of carbohydrate epitopes and potential uses for targeted cancer immunotherapies. / Dingjan, Tamir; Spendlove, Ian; Durrant, Lindy G; Scott, Andrew M; Yuriev, Elizabeth; Ramsland, Paul A.

In: Molecular Immunology, Vol. 67, No. 2, 2015, p. 75-88.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Dingjan, Tamir

AU - Spendlove, Ian

AU - Durrant, Lindy G

AU - Scott, Andrew M

AU - Yuriev, Elizabeth

AU - Ramsland, Paul A

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KW - Blood group carbohydrates

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