The immunocytokine NHS-IL12 as a potential cancer therapeutic

摘要: // Jonathan Fallon 1,* , Robert Tighe 2,* Giorgio Kradjian 2 Wilson Guzman Anna Bernhardt Berend Neuteboom Yan Lan Helen Sabzevari Jeffrey Schlom 1 John W. Greiner Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Institute, Bethesda, Maryland USA; EMD Serono Research Development Billerica, Massachusetts USA * These authors contributed equally to this work. Correspondence: Schlom, email: Keywords : immunocytokine, interleukin-12, tumor necrosis therapy, T cells, immunotherapy Received February 19, 2014 Accepted March 23, Published 24, Abstract Targeted delivery IL-12 might turn cytokine into a safer, more effective cancer therapeutic. Here we describe novel NHS-IL12, consisting two molecules fused necrosis-targeting human IgG1 (NHS76). The addition the moiety resulted in longer plasma half-life NHS-IL12 than recombinant IL-12, selective targeting murine tumors vivo . Data from both vitro assays using PBMCs primate studies showed that IFN-gamma production by immune cells is attenuated following treatment with suggesting an improved toxicity profile seen alone. was superior when evaluated as anti-tumor agent three models. Mechanistic utilizing cell subset-depleting antibodies, flow cytometric methods, cytotoxicity ELISA all indicated effects were primarily CD8+ cell-dependent likely IL-12-mediated. Combining vaccine, radiation, or chemotherapy greater each individual therapy preclinical findings provide rationale clinical testing single combination vaccines, radiation chemotherapy.