Tumor regression in mice following vaccination with human papillomavirus E7 recombinant protein in PROVAX.
Induction of CD8+ cytotoxic T lymphocytes (CTLs) specific for human papillomavirus (HPV) antigens provides an attractive strategy for immunotherapy of HPV-related cancers in humans. In this study, we investigated the potential of utilizing soluble E7 protein of HPV 16 in an adjuvant formulation, PROVAX as a vaccine against a progressively growing E7 transfected K1735-X21 (H-2k) metastatic melanoma cells (HOPE2) in a mouse model. Vaccination of HOPE2 tumor bearing mice (C3H) with E7 protein in PROVAX resulted in significant inhibition of tumor growth, compared to mice vaccinated with E7 in Alum or saline. In vivo depletion of CD8+ or CD4+ cells indicated that CD8+ cells are the major effector cells in mediating the anti-tumor activity in this model. Furthermore, E7-specific CTL activity in vitro was detected in tumor bearing mice vaccinated with E7-PROVAX. Our studies suggest that recombinant HPV antigens in combination with PROVAX could serve as an effective subunit vaccine to stimulate tumor specific CD8+ T cell mediated immunity against HPV-related cancers.
Hariharan
K
K
IDEC Pharmaceuticals Corporation, San Diego, CA 92121, USA.
Braslawsky
G
G
Barnett
R S
RS
Berquist
L G
LG
Huynh
T
T
Hanna
N
N
Black
A
A
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015870:Gene Expression / Q000235:genetics; D007111:Immunity, Cellular / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D014611:Vaccination; D014765:Viral Vaccines / Q000737:chemistry / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16