Targeted cytokines for cancer immunotherapy.
Targeting of cytokines into the tumor microenvironment using antibody-cytokine fusion proteins, called immunocytokines, represents a novel approach in cancer immunotherapy. This article summarizes therapeutic efficacy and immune mechanisms involved in targeting interleukin-2 (IL-2) to neuroectodermal tumors using ganglioside GD2-specific antibody-IL-2 fusion protein (ch14.18-IL-2). Treatment of established melanoma metastases with ch14.18-IL-2 resulted in eradication of disease followed by a vaccination effect protecting mice from lethal challenges with wild-type tumor calls. In a syngeneic neuroblastoma model, targeted IL-2 was effective in the amplification of a weak memory immune response previously induced by IL-12 gene therapy using an engineered linear version of this heterodimeric cytokine. These findings show that targeted IL-2 may provide an effective tool in cancer immunotherapy and establish the missing link between T cell-mediated vaccination and objective clinical responses.
Lode
H N
HN
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Reisfeld
R A
RA
D000818:Animals; D015316:Genetic Therapy; D007167:Immunotherapy; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy
D007376:Interleukin-2