First-in-human phase I trial of NHS-IL12 in advanced solid tumors.

TPS2617 Background: NHS-IL12 is an antibody-cytokine conjugate consisting of two heterodimers of interleukin (IL)-12, fused to a human monoclonal antibody specific for DNA-histone H1 complex exposed in tumor necrosis. IL12 is a proinflammatory cytokine, produced by activated phagocytes and dendritic cells, that plays a critical role in regulating the transition from innate to adaptive immunity. Early clinical trials of IL12 reported clinical responses in metastatic renal cell carcinoma, Kaposi sarcoma (50–71% response rate), T-cell lymphoma (56%), and non-Hodgkin’s lymphoma (21%). However, systemic toxicity limited further clinical development. NHS-IL12 is designed to reduce toxicity associated with systemic administration of IL12 by selectively targeting delivery to necrotic areas of tumors. A fluorescence imaging study of NHS-murine (mu)-IL12 in mice with syngeneic lung carcinoma demonstrated effective targeting by NHS-muIL12. Immunohistochemistry studies further confirmed effective targeting of tumors ...