A nine-amino acid peptide from IL-1beta augments antitumor immune responses induced by protein and DNA vaccines.
The idiotypic determinants of B cell lymphoma provide a tumor-specific Ag and a target for immunotherapy. We have developed several generations of idiotype vaccines that were tested in an animal model, the 38C13 mouse B cell lymphoma. Initially we showed that effective tumor immunity was elicited by the syngeneic Id when it was conjugated to a carrier protein and mixed with an adjuvant. A subsequent generation of Id vaccines eliminated the need for a carrier protein and for an adjuvant by incorporating cytokines into fusion proteins containing the Id. A third generation of vaccines consisting of naked DNA encoding the Id-granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion proteins was equally effective in inducing tumor immunity. To determine whether Ig variable regions, in the absence of constant regions, could be immunotherapeutic in this model, we tested the use of single-chain Fv (scFv). scFv proteins, produced in bacteria, and naked DNA encoding scFv were used in this study. scFv was tested alone or fused to GM-CSF or an immunoenhancing peptide derived from IL-1beta. Here we demonstrate that scFv-GM-CSF was effective only when injected as a protein, not as a DNA vaccine. In contrast, both scFv-IL-1beta peptide fusion protein and naked DNA encoding it induced tumor immunity that protected mice from tumor challenge.
Hakim
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Division of Oncology, Department of Medicine, Stanford University Medical Center, CA 94305, USA.
Levy
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Levy
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D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry; D007128:Immunoglobulin Fragments / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D010455:Peptides / Q000276:immunology; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000951:Antigens, Neoplasm; D007128:Immunoglobulin Fragments; D007130:Immunoglobulin Idiotypes; D007375:Interleukin-1; D010455:Peptides; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C055966:immunoglobulin Fv; D016178:Granulocyte-Macrophage Colony-Stimulating Factor