ISCOMATRIX adjuvant: an adjuvant suitable for use in anticancer vaccines.
Human Papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are associated with cervical cancer development and progression and can therefore be used as target antigens for cancer immunotherapy. In this study we evaluated the immunogenicity in mice, of different vaccine formulations using recombinant HPV16 derived E6E7 or E7GST fusion proteins. When co-administered with ISCOMATRIX adjuvant, these E6E7 proteins consistently induced E7 specific CTL, in vivo tumor protection, antibody and DTH responses. ISCOMATRIX adjuvant has been developed for use in the formulation of novel human vaccines and has been evaluated for safety and toxicity in human trials. A formulation containing aluminum hydroxide (Al(OH)3) gave a lesser degree of E7 specific antibody, and no local E7 specific CTL response but similar DTH and tumor protection. These findings demonstrate the potential of ISCOMATRIX adjuvant to stimulate both cellular and humoral immune responses to endogenously processed target antigens, and hence is the preferred adjuvant when CTL responses are desirable.
Stewart
Trina J
TJ
Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
Drane
Debbie
D
Malliaros
Jim
J
Elmer
Heidi
H
Malcolm
Karen M
KM
Cox
John C
JC
Edwards
Stirling J
SJ
Frazer
Ian H
IH
Fernando
Germain J P
GJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000912:Antibodies, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D002784:Cholesterol / Q000494:pharmacology*; D002860:Chromium Radioisotopes; D004338:Drug Combinations; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control; D009856:Oncogene Proteins, Viral / Q000276:immunology; D010743:Phospholipids / Q000494:pharmacology*; D012097:Repressor Proteins / Q000276:immunology; D012503:Saponins / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D002860:Chromium Radioisotopes; D004338:Drug Combinations; C068651:E6 protein, Human papillomavirus type 16; C493786:ISCOMATRIX; D009856:Oncogene Proteins, Viral; D010743:Phospholipids; D012097:Repressor Proteins; D012503:Saponins; D014614:Vaccines, Synthetic; C041524:aluminum sulfate; D002784:Cholesterol