Targeted cytokines for cancer immunotherapy

Targeting of cytokines into the tumor microenvironment using antibody-cytok ine fusion proteins, called immunocytokines, represents a novel approach in cancer immunotherapy. This article summarizes therapeutic efficacy and imm une mechanisms involved in targeting interleukin-2 (IL-2) to neuroectoderma l tumors using ganglioside GD2-specific antibody-IL-2 fusion protein (ch14. 18-IL-2). Treatment of established melanoma metastases with ch14.18-IL-2 re sulted in eradication of disease followed by a vaccination effect protectin g mice from lethal challenges with wild-type tumor calls. In a syngeneic ne uroblastoma model, targeted IL-2 was effective in the amplification of a we ak memory immune response previously induced by IL-12 gene therapy using an engineered linear version of this heterodimeric cytokine. These findings s how that targeted IL-2 may provide an effective tool in cancer immunotherap y and establish the missing link between T cell-mediated vaccination and ob jective clinical responses.