Carbohydrate vaccines as immunotherapy for cancer.
Carbohydrates have established themselves as the most clinically relevant antigens of those tested and subsequently developed for vaccines against infectious diseases. However, in cancer patients, many of the defined carbohydrate antigens are really altered 'self' antigens and for unclear reasons, the body does not react to them immunologically. Although these self antigens have been found to be potentially suitable targets for immune recognition and killing, the development of vaccines for cancer treatment is actually more challenging compared with those for infectious diseases mainly because of the difficulty associated with breaking the body's immunological tolerance to the antigen. These antigens lack the inherent immunogenicity associated with bacterial antigens and, therefore, methods to enhance immunological recognition and induction of immunity in vivo are under investigation. These include defining the appropriate tumour-associated antigen, successfully synthesizing the antigen to mimic the original molecule, inducing an immune response, and subsequently enhancing the immunological reactivity so that all components can work together. This has been successfully accomplished with several glycolipid and glycoprotein antigens using carriers such as keyhole limpet haemocyanin (KLH) together with a saponin adjuvant, QS-21. Not only can high titre IgM and IgG antibodies be induced, which are specific for the antigen used for immunization, but the antibodies can mediate complement lysis. The approaches for synthesis, conjugation, clinical administration and immunological potential are discussed.
Slovin
Susan F
SF
Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York 10021, USA. slovins@mskcc.org
Keding
Stacy J
SJ
Ragupathi
Govind
G
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000628:therapy*; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D018074:Vaccines, Conjugate