Coexpression of interleukin-4 and B7.1 in murine tumor cells leads to improved tumor rejection and vaccine effect compared to single gene transfectants and a classical adjuvant.
To improve the vaccine potency of gene-modified tumor cells, using retroviruses, we have expressed the B7.1 gene in J558L cells and a subline previously transfected with the gene for interleukin-4 (IL-4). Complete longterm tumor eradication occurred in only 73-82% of syngeneic BALB/c mice injected with IL-4 or B7.1 transfectants or tumor cells mixed with the adjuvant Corynebacterium parvum. In contrast, none of the mice injected with J558-IL4/B7.1 cells developed a tumor, thus demonstrating that IL-4 and B7.1 together induced a more potent antitumor immune response compared to either molecule alone. Immunization/challenge experiments demonstrated that IL-4/B7.1 co-transfected cells possessed improved and tumor-specific vaccine potency when compared to single gene transfectants and, more importantly, to a tumor cell/C. parvum mixture. Furthermore, irradiation of vaccine cells almost completely abrogated the vaccine effect. Together, our results mean a step toward an improved tumor cell vaccine that acquires efficacy by the concerted action of IL-4 and B7.1 and the use of viable cells.
Cayeux
S
S
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Beck
C
C
Dörken
B
B
Blankenstein
T
T
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology; D005260:Female; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D011425:Propionibacterium acnes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014612:Vaccines / Q000235:genetics* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D014612:Vaccines; D014614:Vaccines, Synthetic; D015847:Interleukin-4