ISCOM based vaccines for cancer immunotherapy.
Immunostimulating complex (ISCOM) vaccines are particulate antigen delivery vehicles composed of saponin, cholesterol, phospholipid and immunogen. Here we illustrate that ISCOM-based vaccines represent an attractive modality for the development of anti-cancer vaccines. Using murine models and a model cancer antigen, ISCOM vaccines were shown to induce potent CD8 T cell responses, to mediate protection in three different tumor models, to promote Th1-biased immunity, and to induce CD8 T cell responses in the absence of CD4+ T cell help. The former three activities were also found to be substantially improved when the vaccine antigen was associated with the ISCOM structure. Furthermore, the presence in vivo of pre-existing antibodies against the vaccine antigen did not inhibit CD8 T cell induction by the ISCOM vaccine. Although vaccination was effective against challenge with vaccine-antigen expressing tumors, no activity against neighboring vaccine-antigen negative tumor cells was observed, indicating that determinant spreading or bystander activity does not lead to significant anti-cancer activity.
Lenarczyk
Aleksandra
A
Cooperative Research Center for Vaccine Technology, Queensland Institute of Medical Research and the University of Queensland, Queensland 4029, Australia.
Le
Thuy T T
TT
Drane
Debbie
D
Malliaros
Jim
J
Pearse
Martin
M
Hamilton
Ross
R
Cox
John
J
Luft
Thomas
T
Gardner
Joy
J
Suhrbier
Andreas
A
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000517:prevention & control; D000939:Epitopes; D005260:Female; D016882:ISCOMs / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007279:Injections, Subcutaneous; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D013997:Time Factors; D014611:Vaccination
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D016882:ISCOMs; D007074:Immunoglobulin G; D010047:Ovalbumin