Anti-tumor efficacy and pre-clinical immunogenicity of IFNα2a-NGR

Regul Toxicol Pharmacol. 2011 Jun;60(1):73-8. doi: 10.1016/j.yrtph.2011.02.007. Epub 2011 Feb 19.

Abstract

Previously studies have shown that tumor-homing peptide NGR enhances the therapeutic efficacy of human interferon α2a (IFNα2a) against tumors. Here we investigated in vivo anti-tumor effect of recombinant human IFNα2a-NGR (rhIFNα2a-NGR) against human lung adenocarcinoma cell line SPC-A-1, A549 and murine Lewis lung carcinoma (LLC) subcutaneously xenografted tumors and further assessed the immunogenicity of rhIFNα2a-NGR in Sprague Dawley (SD) rats and rhesus monkeys. We found that rhIFNα2a-NGR significantly inhibited the growth of SPC-A-1, A549 and LLC cells-xenografted tumors in a dose-dependent manner. Although the antibodies to rhIFNα were detected in the serum of SD rats and rhesus monkeys treated with rhIFNα2a-NGR, these antibodies did not cause obvious pathological consequence. Taken together, these data demonstrate that rhIFNα2a-NGR has obvious anti-tumor efficacy in vivo, perhaps due to the tumor-homing peptide NGR. Thus rhIFNα2a-NGR represents a promising novel drug for effective treatment of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / genetics*
  • Interferon-alpha / immunology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Macaca mulatta
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oligopeptides / genetics*
  • Oligopeptides / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Immunologic / genetics*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Proteins
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Interferon alpha-2
  • Interferon-alpha
  • NGR peptide
  • Oligopeptides
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Recombinant Proteins