COEXPRESSION OF INTERLEUKIN-4 AND B7.1 IN MURINE TUMOR-CELLS LEADS TOIMPROVED 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 ret roviruses, we have expressed the B7.1 gene in J558L cells and a sublin e previously transfected with the gene for interleukin-4 (IL-4). Compl ete longterm tumor eradication occurred in only 73-82% of syngeneic BA LB/c mice injected with IL-4 or B7.1 transfectants or tumor cells mixe d with the adjuvant Corynebacterium parvum. In contrast, none of the m ice injected with J558-IL4/B7.1 cells developed a tumor, thus demonstr ating that IL-4 and B7.1 together induced a more potent antitumor immu ne 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 g ene transfectants and, more importantly, to a tumor cell/C. parvum mix ture. Furthermore, irradiation of vaccine cells almost completely abro gated the vaccine effect. Together, our results mean a step toward an improved tumor cell vaccine that acquires efficacy by the concerted ac tion of IL-4 and B7.1 and the use of viable cells.