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.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
authors.forename: Tamir
authors.initials: T
authors.lastname: Dingjan
authors.affiliation: Academic Department of Clinical Oncology, Division of Cancer and Stem cells, University of Nottingham, City Hospital, Nottingham NG5 1PB, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Spendlove
authors.affiliation: Academic Department of Clinical Oncology, Division of Cancer and Stem cells, University of Nottingham, City Hospital, Nottingham NG5 1PB, United Kingdom.
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
authors.affiliation: Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia; Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia. Electronic address: elizabeth.yuriev@monash.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yuriev
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, VIC 3004, Australia; Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Surgery Austin Health, University of Melbourne, Heidelberg, VIC 3084, Australia; School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Perth, WA 6845, Australia. Electronic address: pramsland@burnet.edu.au.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Ramsland
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007983:Lewis Blood Group Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000906:Antibodies; D002241:Carbohydrates; D000939:Epitopes; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen
keywords: Antibody tumor targeting; Blood group carbohydrates; Cancer immunotherapy; Carbohydrate conformations; Carbohydrate recognition; Protein–carbohydrate interactions