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

ABSTRACT 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 long-term 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 t...