Synthetic carbohydrate-based anticancer vaccines: the Memorial Sloan-Kettering experience.
Malignantly transformed cells can express aberrant cell surface glycosylation patterns, which serve to distinguish them from normal cells. This phenotype provides an opportunity for the development of carbohydrate-based vaccines for cancer immunotherapy. Synthetic carbohydrate-based vaccines, properly introduced through vaccination of a subject with a suitable construct, should be recognized by the immune system. Antibodies induced against these carbohydrate antigens could then participate in the eradication of carbohydrate-displaying tumor cells. Advances in carbohydrate synthetic capabilities have allowed us to efficiently prepare a range of complex, synthetic anticancer vaccine candidates. We describe herein the progression of our longstanding carbohydrate-based anticancer vaccine program, which is now at the threshold of clinical evaluation in several contexts. Our carbohydrate-based anticancer vaccine program has evolved through a number of stages: monomeric vaccines, monomeric clustered vaccines, unimolecular multi-antigenic vaccines and dual-acting vaccines. This account will focus on our recently developed unimolecular multi-antigenic constructs and potential dual-acting constructs, which contain clusters of both carbohydrate and peptide epitopes.
Zhu
Jianglong
J
Research Fellow, Bioorganic Chemistry Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. zhuj@mskcc.org
Warren
J David
JD
Danishefsky
Samuel J
SJ
D000818:Animals; D000906:Antibodies / Q000097:blood; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000276:immunology*; D002236:Carbohydrate Conformation; D015195:Drug Design; D000939:Epitopes; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016730:Program Development; D013329:Structure-Activity Relationship
D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D000939:Epitopes