Cytokines such as interferons and interleukins are administered for cancer because of their broad-based immunostimulatory effects including generation of tumor-reactive lymphocytes (11). Interleukin-2 (IL-2), or aldesleukin, which is indicated for the treatment of adults with metastatic renal cell carcinoma and melanoma, is the most studied cytokine. IL-2 dose-dependently activates cellular immunity and causes release of other immune-boosting cytokines in vivo (11). Systemic cytokine therapy is generally limited by rapid degradation and elimination of the cytokine, the inability to achieve optimal concentrations in the tumor microenvironment, and dose-dependent toxicity, including life-threatening side effects such as vascular leak syndrome and orthostatic hypotension (12-15). Cytokine gene therapy, in which a cytokine gene (such as that for IL-2) is introduced into tumor cells, is being explored to overcome some of these limitations of systemic cytokine administration. However, cytokine gene therapy is technologically challenging and resource-intensive.
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