NATURAL-KILLER-CELLS AND GENE-THERAPY - POTENTIAL OF GENE TRANSFECTION FOR OPTIMIZING EFFECTOR CELL FUNCTIONS AND FOR TARGETING GENE-PRODUCTS INTO TUMOR-METASTASES

Fluorescently labeled, adoptively transferred interleukin (IL)-2 activ ated natural killer (A-NK) cells have the ability to selectively accum ulate within established pulmonary or hepatic metastases, binding to t umor cells and/or to microvascular endothelial cells. A-NK cells have also been shown to exert antimetastatic therapy in animal models and i n the clinic. Transfection of genes for cytokines or possibly other mo lecules has the potential to improve the therapeutic potency and effic acy of the effector cells. Gene transfection to induce autocrine produ ction of IL-2 and/or other cytokines is expected to augment their anti metastatic activities, while avoiding toxicity from systemic administr ation of high doses of cytokines. An alternative or complementary stra tegy for gene therapy is to transfect A-NK cells with genes for cytoto xic molecules, to selectively target them to metastatic sites.