Synthetic carbohydrate-based antitumor vaccines: challenges and opportunities.
The development of a clinically effective, carbohydrate-based antitumor vaccine is a longstanding ambition in the prevention and treatment of cancer. This review seeks to provide a discussion of some of the unique challenges facing this particular field of immunology. The authors present a historic account of their ongoing research program devoted to the development of fully synthetic, carbohydrate-based anticancer vaccines of clinical value. As will be seen, remarkable advances in carbohydrate and glycopeptide assembly techniques have allowed for the preparation of synthetic constructs of progressively increasing structural complexity. The authors describe the evolution of their synthetic carbohydrate program from first-generation constructs, which were monovalent in nature, to highly complex unimolecular multivalent vaccines, in which multiple carbohydrate antigens are displayed in the context of a single polypeptide backbone. It is the hope that each generation of vaccines represents a move closer to achieving the ultimate objective of developing broadly useful, robust anticancer vaccines.
Ouerfelli
Ouathek
O
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. o-ouerfelli@ski.mskcc.org
Warren
J David
JD
Wilson
Rebecca M
RM
Danishefsky
Samuel J
SJ
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000138:chemical synthesis / Q000276:immunology; D002986:Clinical Trials as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005260:Female; D006020:Glycopeptides / Q000138:chemical synthesis / Q000276:immunology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D018074:Vaccines, Conjugate / Q000276:immunology / Q000627:therapeutic use*; D014614:Vaccines, Synthetic
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D002241:Carbohydrates; C472765:Globo-H; D006020:Glycopeptides; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; C502358:globo H-KLH vaccine