Abstract
Attempts to vaccinate against tumors can be hindered by the induction of immunological tolerance to the target Ag as a result of Ag expression on normal tissues. In this study, we find that transgenic mice expressing the melanoma-associated Ag CD63/ME491/neuroglandular/NKI/C-3 on their normal tissues do, in fact, exhibit immunological tolerance to the Ag, recapitulating the conditions in cancer patients. In these mice, growth of murine melanoma cells expressing the Ag after gene transfer was inhibited by immunization with Ag-expressing recombinant vaccinia virus combined with IL-2, but not by immunization with the protein alone, anti-idiotypic Abs, or irradiated tumor cells. The effect of the recombinant virus was demonstrated both for nonestablished and established tumors. Infiltration with both CD4(+) and CD8(+) T lymphocytes was significantly more extensive in tumors from experimental mice than in tumors from control mice. MHC class I-positive, but not class I-negative, tumors were inhibited by the vaccine, suggesting that MHC class I-restricted T lymphocytes play a role in the antitumor effects. Abs did not appear to be involved in the vaccine effects. CD63 was immunogenic in 2 of 13 melanoma patients, pointing to the potential of this Ag, combined with IL-2, as a vaccine for melanoma patients.
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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Animals
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Antibodies, Neoplasm / biosynthesis
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Antigens, CD / administration & dosage*
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, Neoplasm / administration & dosage*
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Antigens, Neoplasm / genetics
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / immunology
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Antineoplastic Agents / metabolism
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Cancer Vaccines / administration & dosage*
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Cancer Vaccines / biosynthesis
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology
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Female
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Growth Inhibitors / administration & dosage*
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Growth Inhibitors / genetics
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Hemadsorption
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Humans
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Immune Tolerance / genetics
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Immunity, Cellular / genetics
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Interleukin-2 / administration & dosage
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / metabolism
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Melanoma / immunology
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology*
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Melanoma, Experimental / prevention & control*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Organ Specificity / genetics
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Organ Specificity / immunology
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Platelet Membrane Glycoproteins / administration & dosage*
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Platelet Membrane Glycoproteins / biosynthesis
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Platelet Membrane Glycoproteins / genetics
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Platelet Membrane Glycoproteins / immunology
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Species Specificity
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Tetraspanin 30
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Transfection
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Tumor Cells, Cultured
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / biosynthesis
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Vaccines, Synthetic / immunology
Substances
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Antibodies, Neoplasm
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Antigens, CD
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Antigens, Neoplasm
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Antineoplastic Agents
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CD63 protein, human
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Cancer Vaccines
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Cd63 protein, mouse
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Growth Inhibitors
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Interleukin-2
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Platelet Membrane Glycoproteins
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Tetraspanin 30
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Vaccines, Synthetic