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 activated natural killer (A-NK) cells have the ability to selectively accumulate within established pulmonary or hepatic metastases, binding to tumor cells and/or to microvascular endothelial cells. A-NK cells have also been shown to exert antimetastatic therapy in animal models and in the clinic. Transfection of genes for cytokines or possibly other molecules has the potential to improve the therapeutic potency and efficacy of the effector cells. Gene transfection to induce autocrine production of IL-2 and/or other cytokines is expected to augment their antimetastatic activities, while avoiding toxicity from systemic administration of high doses of cytokines. An alternative or complementary strategy for gene therapy is to transfect A-NK cells with genes for cytotoxic molecules, to selectively target them to metastatic sites.