Open AccessNHS-IL12, a Tumor-Targeting Immunocytokine
Author(s) -
John W. Greiner,
Y. Maurice Morillon,
Jeffrey Schlom
Publication year - 2021
Publication title -
immunotargets and therapy
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.256
H-Index - 7
ISSN - 2253-1556
DOI - 10.2147/itt.s306150
Subject(s) - interleukin 12 , medicine , materials science , biology , genetics , in vitro , cytotoxic t cell
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.