CYTOKINE GENE-MODIFIED TUMOR-CELLS FOR PROPHYLACTIC AND THERAPEUTIC VACCINATION - IL-2, IFN-GAMMA, OR COMBINATION IL-2-GAMMA(IFN)

Murine melanoma cells were engineered to express interleukin-2 (IL-2), interferon-gamma (IFN-gamma) or both cytokines at various dose levels by means of the adenovirus-enhanced transferrinfection (AVET) method. The gene-modified cells were tested for their potency to induce an an titumor immune response in two experimental settings with different tu mor load. In a prophylactic vaccination model, both IL-2 and IFN-gamma showed a dose-dependent protection against tumor cell challenge in tw o melanoma models. In the therapeutic vaccination model, where mice wi th measurable tumors were treated, immunization with IL-2 or IFN-gamma gene-modified cells led to complete tumor regression in 30% or 20% of the tumor-bearing animals respectively. The combination of lL-2+IFN-g amma resulted in complete tumor regression in up to 50% of the tumor-b earing mice.