Augmentation of Antitumor Immunity by Tumor Cells Transduced With a Retroviral Vector Carrying the Interleukin-2 and Interferon-y cDNAs

Therapeutic models using gene transfer into tumor cells have pursued three objectives: (1 ) to induce rejection of the tumor transduced with therapeutic genes, (2) to induce immune-mediated regression of metastatic disease, and (3) to induce long-lasting immunity to protect against challenge with tumor cells or clinical regrowth of micrometastatic disease. Because in vivo therapy for patients with cancer using gene transfer would, as a first step, attempt to eliminate the existing tumor, we have investigated whether antitumor immunity induced by tumor cells secreting a single cytokine could be increased by cotransfer of a second cytokine gene. To test this approach, CMS-5, a murine fibrosarcoma, was transduced with retroviral vectors carrying interleukin-2 (IL-2). interferon-7 (IFN-y), or granulocyte-macrophage-colony-stimulating factor (GMCSF) cDNA alone or IL-2 cDNA in combination with IFN-7 or GM-CSF cDNA. Single cytokine-secreting clones were selected to match levels of cytokine production by double