Abstract
The interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 has been implicated in the establishment of cell-mediated immunity as well as humoral immune responses. To examine the role of CD40L in eliciting antitumor immunity, we introduced murine CD40L gene into P815 mastocytoma (CD40L-P815). CD40L-P815 cells underwent prompt rejection when inoculated s.c. into syngenic DBA/2 mice or athymic BALB/c nu/nu mice, which was mediated by NK cells and dependent on endogenous IL-12. The primary rejection of CD40L-P815 cells in DBA/2 mice elicited CD8+ T cell-mediated protective and systemic immunity against parental tumor cells, which was induced by CD4+ T cells and endogenous B7. These results indicated a potent antitumor effect of CD40L that is mediated by potentiation of host Ag-presenting cell functions, and introduction of CD40L will be useful as a new strategy of immuno-gene therapy against tumors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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B7-1 Antigen / biosynthesis
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B7-1 Antigen / physiology*
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CD40 Antigens / biosynthesis
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CD40 Antigens / genetics
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CD40 Antigens / metabolism*
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CD40 Ligand
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Female
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Graft Rejection / immunology
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Immunotherapy, Adoptive / methods
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Interleukin-12 / biosynthesis
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Interleukin-12 / physiology*
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Killer Cells, Natural / immunology
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Ligands
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Lymphocyte Activation / drug effects
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism
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Mast-Cell Sarcoma / immunology*
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Mast-Cell Sarcoma / prevention & control*
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / pharmacology*
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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, Inbred DBA
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Mice, Nude
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Neoplasm Transplantation
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Transfection / immunology
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Up-Regulation / immunology
Substances
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Antineoplastic Agents
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B7-1 Antigen
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CD40 Antigens
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Ligands
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Membrane Glycoproteins
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CD40 Ligand
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Interleukin-12