Enhancement by IL-12 of the cytolytic T lymphocyte (CTL) response of mice immunized with tumor-specific peptides in an adjuvant containing QS21 and MPL.
Immunization of cancer patients with tumor-specific antigenic peptides is currently being tested in several clinical studies. We have examined the induction of CTL responses in mice after various modalities of peptide vaccination, to explore protocols that could be applied to humans. Our first model antigen was P198, which results from a point mutation in a normal gene. While two immunizations with peptide P198 in SBAS-1c adjuvant induced measurable CTL responses in less than 10% of DBA/2 mice, the addition of IL-12 to the peptide adjuvant mixture resulted in high CTL responses in nearly all mice. This strong enhancing effect of IL-12 was observed with 1,000 and 300 units and decreased gradually as the doses were reduced to 30 units. When IL-12 was replaced by other cytokines acting on T cells or antigen-presenting cells, such as IFN-gamma, IL-2, IL-6, IL-7, GM-CSF or MCP-3, no significant enhancing effect was observed. The same effect of IL-12 was obtained with peptide P1A, which is a major tumor-specific antigen of mastocytoma P815 and is encoded by a gene that is specifically activated in tumors.
Silla
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Ludwig Institute for Cancer Research, Brussels Branch, 74 Avenue Hippocrate-UCL 74.59, B-1200 Brussels, Belgium.
Fallarino
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Boon
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T
Uyttenhove
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C
D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004357:Drug Synergism; D004431:Ear, External; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D006614:Hindlimb; D006649:Histocompatibility Antigens / Q000276:immunology*; D016233:Immunotherapy, Active; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D008213:Lymphocyte Activation; D012515:Mast-Cell Sarcoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D009928:Organ Specificity; D010446:Peptide Fragments / Q000276:immunology*; D012503:Saponins / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D013623:Tail; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D008050:Lipid A; D010446:Peptide Fragments; D012503:Saponins; C064710:transplantation antigen P198; C076546:tumor rejection antigen P815A, mouse; D018664:Interleukin-12; C078785:saponin QA-21V1; D007371:Interferon-gamma; C048436:monophosphoryl lipid A