quil-a and Thymoma

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.

Topics: Adjuvants, Immunologic; Alum Compounds; Amino Acid Sequence; Animals; Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Disease Models, Animal; Drug Combinations; Epitopes, T-Lymphocyte; Female; Immunity, Active; Inulin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Molecular Sequence Data; Mutagenesis, Site-Directed; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Peptide Fragments; Quillaja Saponins; Saponins; Skin Neoplasms; T-Lymphocytes, Cytotoxic; Th2 Cells; Thymoma; Tumor Cells, Cultured