INFLUENCE OF GENE-MODIFIED (IL-7, IL-4, AND B7) TUMOR-CELL VACCINES ON TUMOR-ANTIGEN PRESENTATION

Tumor cells genetically modified to coexpress certain cytokines (such as IL-7 or IL-4) and B7.1 have increased immunogenicity, Since tumor A gs can be presented either directly by tumor cells or indirectly by ho st APC (cross-priming), we asked whether B7.1 and IL-7 or IL-4 complem ented each other by improving preferentially one or both pathways of A g presentation. We used TS/A (H-2d) tumor cells and their IL-7, B7, an d IL-7/B7 transfectants, and MCA205 (H-2b) tumor cells and their IL-4 and B7 transfectants. beta-galactosidase (beta-gal) was chosen as surr ogate tumor Ag. beta-gal has different predominant MHC class I epitope s in H-2d and H-2b mice. Immunization of(H-2b x d)F-1 mice with TS/A/b eta-gal transfectants showed that both IL-7 and B7.1 and, as control, granulocyte-macrophage CSF augmented cross-priming and rejection of a challenge with MCA205/beta-gal (H-2b). Similarly, immunization with MC A205/beta-gal B7.1 or IL-4 transfectants enhanced cross-priming and re jection of a challenge with TS/A/beta-gal. beta-gal-specific rejection was confirmed by CTL assay. However, direct Ag presentation by tumor cells was enhanced only by B7.1, and not IL-7. For this study, H-2b nu /nu mice reconstituted with F-1 lymphocytes were immunized with H-2d T S/A/beta-gal transfectants and challenged with TS/A/beta-gal. In concl usion, indirect Ag presentation was augmented by B7, IL-7, and IL-4, w hile direct Ag presentation was improved only by B7.