ISCOMATRIX™ adjuvant: an adjuvant suitable for use in anticancer vaccines

• Published in: Vaccine 2004-09, Vol.22 (27), p.3738-3743
• Main Authors: Stewart, Trina J, Drane, Debbie, Malliaros, Jim, Elmer, Heidi, Malcolm, Karen M, Cox, John C, Edwards, Stirling J, Frazer, Ian H, Fernando, Germain J.P
• Format: Article
• Language: English
• Subjects: Adjuvant; Adjuvants, Immunologic - pharmacology; Alum Compounds - pharmacology; Aluminum; Animal vaccines; Animals; Antibodies, Neoplasm - analysis; Antibodies, Neoplasm - biosynthesis; Antibody Formation - immunology; Applied microbiology; Biological and medical sciences; Cancer vaccine; Cancer Vaccines - immunology; Cell Line; Cervical cancer; Cholesterol - pharmacology; Chromium Radioisotopes; Drug Combinations; E coli; Female; Fundamental and applied biological sciences. Psychology; Human papillomavirus; Human papillomavirus 16; Hypersensitivity, Delayed - immunology; Immune system; Immunogenicity; Immunotherapy; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Neoplasm Transplantation; Neoplasms, Experimental - prevention & control; Oncogene Proteins, Viral - immunology; Phospholipids - pharmacology; Proteins; Repressor Proteins - immunology; Saponins - pharmacology; T-Lymphocytes, Cytotoxic - immunology; Th1 Cells - immunology; Th2 Cells - immunology; Tumor protection; Tumors; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - immunology; Viral infections
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.03.026

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.