The immunocytokine NHS-IL12 as a potential cancer therapeutic

Oncotarget. 2014 Apr 15;5(7):1869-84. doi: 10.18632/oncotarget.1853.


Targeted delivery of IL-12 might turn this cytokine into a safer, more effective cancer therapeutic. Here we describe a novel immunocytokine, NHS-IL12, consisting of two molecules of IL-12 fused to a tumor necrosis-targeting human IgG1 (NHS76). The addition of the human IgG1 moiety resulted in a longer plasma half-life of NHS-IL12 than recombinant IL-12, and a selective targeting to murine tumors in vivo. Data from both in vitro assays using human PBMCs and in vivo primate studies showed that IFN-gamma production by immune cells is attenuated following treatment with the immunocytokine, suggesting an improved toxicity profile than seen with recombinant IL-12 alone. NHS-IL12 was superior to recombinant IL-12 when evaluated as an anti-tumor agent in three murine tumor models. Mechanistic studies utilizing immune cell subset-depleting antibodies, flow cytometric methods, and in vitro cytotoxicity and ELISA assays all indicated that the anti-tumor effects of NHS-IL12 were primarily CD8+ T cell-dependent and likely IL-12-mediated. Combining NHS-IL12 treatment with a cancer vaccine, radiation, or chemotherapy resulted in greater anti-tumor effects than each individual therapy alone. These preclinical findings provide a rationale for the clinical testing of this immunocytokine, both as a single agent and in combination with vaccines, radiation and chemotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / immunology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • Docetaxel
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology*
  • Immunoglobulin G / therapeutic use
  • Immunomodulation
  • Indoles / administration & dosage
  • Interferon-gamma / metabolism*
  • Interleukin-12 / immunology
  • Interleukin-12 / pharmacology*
  • Interleukin-12 / therapeutic use
  • Lymphocyte Activation / drug effects
  • Macaca fascicularis
  • Membrane Glycoproteins / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / therapy*
  • Protein Engineering
  • Pyrroles / administration & dosage
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Fusion Proteins / therapeutic use
  • Sunitinib
  • Survival Rate
  • Taxoids / administration & dosage
  • Tumor Burden


  • Cancer Vaccines
  • Immunoglobulin G
  • Indoles
  • L-BLP25
  • Membrane Glycoproteins
  • NHS-IL12 immunocytokine
  • Pyrroles
  • Recombinant Fusion Proteins
  • Taxoids
  • Docetaxel
  • Interleukin-12
  • Interferon-gamma
  • Sunitinib