A 9-AMINO ACID PEPTIDE FROM IL-1-BETA 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 generati ons of idiotype vaccines that were tested in an animal model, the 38C1 3 mouse B cell lymphoma. Intitially we showed that effective tumor imm unity was elicited by the syngeneic Id when it was conjugated to a car rier protein and mixed with an adjuvant, A subsequent generation of Id vaccines eliminated the need for a carrier protein and for an adjuvan t 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 prote ins was equally effective in inducing tumor immunity. To determine whe ther 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 sc Fv were used in this study. scFv was tested alone or fused to CM-CSF o r an immunoenhancing peptide derived from IL-1 beta. Here we demonstra te that scFv-CM-CSF was effective only when injected as a protein, not as a DNA vaccine. In contrast, both scFv-IL-1 beta peptide fusion pro tein and naked DNA encoding it induced tumor immunity that protected m ice from tumor challenge.