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

• Published in: Molecular immunology Vol. 67; no. 2; pp. 75 - 88
• Main Authors: Dingjan, Tamir, Spendlove, Ian, Durrant, Lindy G., Scott, Andrew M., Yuriev, Elizabeth, Ramsland, Paul A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2015
• Subjects: Antibodies - immunology; Antibodies - metabolism; Antibodies - therapeutic use; Antibody tumor targeting; Blood group carbohydrates; Cancer immunotherapy; Carbohydrate Conformation; Carbohydrate conformations; Carbohydrate recognition; Carbohydrate Sequence; Carbohydrates - chemistry; Carbohydrates - immunology; Epitopes - chemistry; Epitopes - immunology; Epitopes - metabolism; Humans; Immunotherapy - methods; Lewis Blood Group Antigens - chemistry; Lewis Blood Group Antigens - immunology; Lewis Blood Group Antigens - metabolism; Molecular Sequence Data; Neoplasms - immunology; Neoplasms - therapy; Protein–carbohydrate interactions; CDC; Fab; Antibody tumor targeting; Protein–carbohydrate interactions; H; L; TACA; Cancer immunotherapy; PDB; CDR; TF or T; Carbohydrate recognition; V; Blood group carbohydrates; Le; Tn; Carbohydrate conformations; ADCC
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2015.02.028

•Dramatic glycosylation changes occur with carcinogenesis and cancer progression.•Tumor-associated carbohydrate antigens are candidates for targeting by antibodies.•Antibodies can envelop the whole epitope to recognize Lewis carbohydrates.•Lewis epitopes display similar and relatively rigid three-dimensional structures.•Glycan structural data may be useful for the design of new antibody therapeutics. 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.