Plant viral genes in DNA idiotypic vaccines activate linked CD4(+) T-cell mediated immunity against B-cell malignancies

DNA delivery of tumor antigens can activate specific immune attack on cance r cells. However, antigens may be weak, and immune capacity can be compromi sed. Fusion of genes encoding activating sequences to the tumor antigen seq uence facilitates promotion and manipulation of effector pathways. Idiotypi c determinants of B-cell tumors, encoded by the variable region genes, are clone-specific tumor antigens. When assembled as single-chain Fv (ScFv) alo ne in a DNA vaccine, immunogenicity is low. Previously, we found that fusio n of a sequence from tetanus toxin (fragment C; FrC) promoted anti-idiotypi c protection against lymphoma and myeloma. We have now investigated an alte rnative fusion gene derived from a plant virus, potato virus X coat protein , a primary antigen in humans. When fused to scFv, the self-aggregating pro tein generates protection against lymphoma and myeloma. In contrast to scFv -FrC, protection against lymphoma is mediated by CD4(+) T cells, as is prot ection against myeloma. Plant viral proteins offer new opportunities to act ivate immunity against linked T-cell epitopes to attack cancer.