What to do with targeted IL-2

A common strategy in immunotherapy of cancer is the induction of an increas ed immunogenicity of syngeneic malignancies. A novel approach to achieve th is goal is the targeting of cytokines into the tumor microenvironment with antibody-cytokine fusion proteins, called immunocytokines. This report summ arizes therapeutic efficacy and immune mechanisms involved in targeting IL- 2 to syngeneic tumors and describes their extended use as a synergistic tre atment modality for cancer vaccines and antiangiogenesis. Treatment of esta blished melanoma and colon carcinoma metastases with IL-2 immunocytokines r esulted in eradication of disease, followed by a vaccination effect protect ing mice from lethal challenges with wild-type tumor cells. In a syngeneic neuroblastoma model, targeted IL-2 elicited effective antitumor responses m ediated by NK cells in the absence of a T-cell memory. Interestingly, targe ted IL-2 was effective in amplification of memory immune responses previous ly induced by cancer vaccines. Furthermore, a synergistic effect achieved b y combining targeted IL-2-immunotherapy with an antiangiogenic inhibitor of integrin alpha(v)beta(3) extends the potential of this immunotherapeutic s trategy in combination with antiangiogenesis as demonstrated in three synge neic tumor models. Based on these findings, targeted IL-2 may provide an ef fective tool for the adjuvant treatment of cancer either applied as a singl e strategy or in combination with cancer vaccines and antiangiogenic strate gies. (C) 2000 Prous Science. All rights reserved.