Abstract
Many cervical cancers express the E7 protein of human papillomavirus 16 as a tumor-specific Ag (TSA). To establish the role of E7-specific T cell help in CD8+ CTL-mediated tumor regression, C57BL/6J mice were immunized with E7 protein or with a peptide (GF001) comprising a minimal CTL epitope of E7, together with different adjuvants. Immunized mice were challenged with an E7-expressing tumor cell line, EL4.E7. Growth of EL4.E7 was reduced following immunization with E7 and Quil-A (an adjuvant that induced a Th1-type response to E7) or with GF001 and Quil-A. Depletion of CD8+ cells, but not CD4+ cells, from an immunized animal abrogated protection, confirming that E7-specific CTL are necessary and sufficient for TSA-specific protection in this model. Immunization with E7 and Algammulin (an alum-based adjuvant) induced a Th2-like response and provided no tumor protection. To investigate whether a Th2 T helper response to E7 could prevent the development of an E7-specific CTL-mediated protection, mice were simultaneously immunized with E7/Algammulin and GF001/Quil-A or, alternatively, were immunized with GF001/Quil-A 8 wk after immunization with E7/Algammulin. Tumor protection was observed in each case. We conclude that an established Th2 response to a TSA does not prevent the development of TSA-specific tumor protective CTL.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Alum Compounds
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Amino Acid Sequence
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Animals
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Antigens, Neoplasm / biosynthesis
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cytotoxicity, Immunologic / immunology*
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Disease Models, Animal
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Drug Combinations
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Female
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Immunity, Active
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Inulin / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Nude
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Oncogene Proteins, Viral / biosynthesis
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology
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Papillomaviridae / immunology
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Papillomavirus E7 Proteins
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Peptide Fragments / immunology
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Quillaja Saponins
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Saponins / immunology
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Skin Neoplasms / genetics
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Skin Neoplasms / immunology
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Skin Neoplasms / prevention & control
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T-Lymphocytes, Cytotoxic / immunology*
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Th2 Cells / immunology*
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Thymoma / genetics
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Thymoma / immunology*
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Thymoma / prevention & control*
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Tumor Cells, Cultured
Substances
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Adjuvants, Immunologic
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Algammulin
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Alum Compounds
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Antigens, Neoplasm
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Drug Combinations
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Epitopes, T-Lymphocyte
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Peptide Fragments
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Quillaja Saponins
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Saponins
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oncogene protein E7, Human papillomavirus type 16
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Quil A
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Inulin