Antitumor effects of a tumor cell vaccine expressing a membrane-bound form of the IL-12 p35 subunit.

AbstractWe investigated whether expression of the IL-12 p35 subunit in membrane-bound form in tumor cells enhanced their immunogenicity. Since p35 is only secreted when associated with the IL-12 p40 subunit, we generated tumor cells expressing membrane-bound forms of p35 and p40 as chimeras with the transmembrane/cytoplasmic region of TNFα (mbIL-12p35 and mbIL-12p40). The relevant vectors were transfected into MethA fibrosarcoma cells, and mbIL-12p35 or mbIL-12p40-expressing tumor clones were isolated and their ability to induce anti-tumor immunity studied. Cells of the mbIL-12p35 tumor clone induced CD69 expression and IFN-γ production in purified CD8+ T cells in vitro, and their in vivo tumorigenicity was reduced. Cells of the mbIL-12p40 tumor clone failed to show either of these activities. Mice that had rejected cells of the mbIL-12p35 tumor clone possessed systemic anti-tumor immunity to wild type tumor cells. The growth rate of mbIL-12p35 tumor cells was greater in CD8+ T cell-depleted mice than in ...