David H. Kirn, Editor infiltrates in regressing tumors, assaying cytotoxic T lymphocytes, and monitoring long-term resistance to tumor growth. The first experimental models and clinical applications of cytokine gene therapy used IL-2 (9). In most experimental systems, the expression of IL-2 by weakly immunogenic tumor cells resulted in growth inhibition of tumor mass. The inhibitory effect is dose dependent, and the degree of suppression of growth correlates directly with the amount of IL-2 produced by the tumor cells (10). Transgenes encoding several other ILs (IL-1, IL-4, IL-6, IL-7, IL-12, and IL-13), IFNs (IFN-γ and IFN-α), hematopoietic growth factors (GM-CSF, G-CSF, and M-CSF), and TNF have also shown promising tumoricidal effects, apparently by different effector mechanisms than IL-2. Although rejection of established tumors occurred in only some of these experimental systems (11), these promising results established the basic biologic value of gene therapy with cytokine-secreting cells that are now applied in clinical trials. More than 60% of recent cytokine-supported clinical cancer gene therapy trials use IL-2; in others, IL-4,-7, and-12; IFN-γ; GM-CSF; or TNF are administered individually or in combination (12).