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 Ags can be presented either directly by tumor cells or indirectly by host APC (cross-priming), we asked whether B7.1 and IL-7 or IL-4 complemented each other by improving preferentially one or both pathways of Ag presentation. We used TS/A (H-2d) tumor cells and their IL-7, B7, and IL-7/B7 transfectants, and MCA205 (H-2b) tumor cells and their IL-4 and B7 transfectants. beta-galactosidase (beta-gal) was chosen as surrogate tumor Ag. beta-gal has different predominant MHC class I epitopes in H-2d and H-2b mice. Immunization of (H-2b x d)F1 mice with TS/A/beta-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 MCA205/beta-gal B7.1 or IL-4 transfectants enhanced cross-priming and rejection 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 F1 lymphocytes were immunized with H-2d TS/A/beta-gal transfectants and challenged with TS/A/beta-gal. In conclusion, indirect Ag presentation was augmented by B7, IL-7, and IL-4, while direct Ag presentation was improved only by B7.
Cayeux
S
S
Robert-Rössle Clinic, Virchow Klinikum, Medical Faculty of Humboldt University of Berlin, Germany.
Richter
G
G
Noffz
G
G
Dörken
B
B
Blankenstein
T
T
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics*; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D006183:H-2 Antigens / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D006183:H-2 Antigens; D015851:Interleukin-7; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001616:beta-Galactosidase