CYTOKINE GENE-TRANSFER AS A THERAPEUTIC STRATEGY

Cytokine gene therapy for cancer could involve either the direct deliv ery of cytokine genes to established tumours to stimulate their reject ion or the injection of cytokine-secreting tumour cells to stimulate a n immune response that could reduce metastatic disease. To assess the feasibility of the first approach, we have compared the ability of dif ferent cytokine-secreting tumour cells to induce the rejection of admi xed, unmodified cells. While interleukin (IL)-2- or interleukin-4-secr eting tumour cells were ineffective, interferon-gamma (IFN-gamma)-secr eting cells could induce rejection of 10% admixed, unmodified cells. B ecause direct gene delivery to tumours is unlikely to be 100% efficien t, these data suggest that IFN-gamma may be the most suitable of these cytokines for this approach. However, we have demonstrated that injec tion of IL-2-secreting tumour cells, following primary tumour excision , can prevent the development of metastases and prolong survival of ra ts. This suggests that IL-2-secreting tumour cells can be effective in the treatment of metastatic disease.