NHS-IL12, a Tumor-Targeting Immunocytokine

Abstract

John W Greiner, Y Maurice Morillon II, Jeffrey Schlom Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USACorrespondence: Jeffrey SchlomLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Room 8B09, Bethesda, MD, 20892, USATel [phone]Fax [phone]Email [email protected]: NHS-IL12 is a novel immunocytokine designed for delivery of IL-12 to the tumor microenvironment (TME). NHS-IL12 consists of two molecules of IL-12 fused to a human IgG1 (NHS76) recognizing DNA/histone complexes, which are often exposed in the necrotic portions of tumors. Preclinical studies demonstrated the tumor-targeting ability and longer plasma half-life for NHS-IL12 when compared with recombinant IL-12 (rIL-12). NHS-IL12 outperformed rIL-12 in enhancing the proliferation and activation of immune as well as antigen-presenting cells, resulting in a more robust primary immune response. NHS-IL12 also reduced the number and function of suppressive myeloid cells (myeloid derived suppressor cells/macrophages) within the TME. In a murine bladder tumor model, NHS-IL12 administration led to a coordinated increase in host immunity with a reduction of immunosuppressive myeloid cells in the TME resulting in substantial reduction in tumor growth. Several preclinical studies have demonstrated increased overall anti-tumor efficacy when NHS-IL12 was combined with either immune-based therapeutics or chemotherapeutic approaches.Keywords: interleukin-12, NHS-IL12, immunotherapy, cancer, immuno-oncology, review

Keywords

• interleukin-12
• nhs-il12
• immunotherapy
• cancer
• immuno-oncology
• review.