Nonviral interferon alpha gene therapy inhibits growth of established tumors by eliciting a systemic immune response

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Updated: Oct 27, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

M Coleman1, S Muller, A Quezada

  • 1GeneMedicine, Inc., The Woodlands, TX 77381-4248, USA.

Human Gene Therapy
|October 30, 1998
PubMed

Insights

This study shows that interferon-alpha (IFN-alpha) gene therapy, delivered via a PINC system, effectively inhibited tumor growth in mice. This immunotherapy activated the immune system, leading to long-term tumor resistance in some animals.

Area of Science:

  • * Immunotherapy and Gene Therapy
  • * Oncology and Tumor Immunology

Background:

  • * Established tumors, including renal cell carcinoma (Renca) and mammary adenocarcinoma (TS/A), were targeted for treatment.
  • * A plasmid expression system encoding murine interferon-alpha4 (IFN-alpha4) was utilized.
  • * The IFN-alpha4 plasmid was complexed with a protective interactive noncondensing polymeric (PINC) delivery system for enhanced stability and efficacy.

Purpose of the Study:

  • * To evaluate the in vivo efficacy of IFN-alpha gene therapy using a PINC delivery system against murine tumors.
  • * To investigate the immunological mechanisms underlying the observed antitumor responses.
  • * To assess the development of immune memory following successful treatment.

Main Methods:

  • * Mice with established Renca and TS/A tumors received intratumoral injections of IFN-alpha/polyvinylpyrrolidone (PVP) expression complexes.
  • * Dose-optimization studies were conducted using 96 microg for Renca and 48 microg for TS/A.
  • * Immune cell depletion studies (CD8+ and CD4+ T cells) were performed to elucidate the immune response pathways.

Main Results:

  • * IFN-alpha/PVP treatment resulted in up to 100% inhibition of tumor growth.
  • * Complete tumor eradication was achieved in 30% of Renca-treated and 10% of TS/A-treated mice.
  • * Antitumor activity was dependent on CD8+ T cells, while CD4+ T cell depletion enhanced tumor rejection.

Conclusions:

  • * IFN-alpha gene therapy, delivered via PINC, is a potent strategy for inducing in vivo antitumor immunity.
  • * The therapy establishes immune memory, conferring resistance to subsequent tumor challenges.
  • * This approach holds promise for developing effective cancer immunotherapies.

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