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Gene therapy with GM-CSF, interleukin-4 and herpes simplex virus thymidine kinase shows strong antitumor effect on

Kyung-Ho Park1, Gyesu Kim, Seung Hun Jang

  • 1Department of Internal Medicine, Seoul National University College of Medicine, Gene Therapy Laboratory of Clinical Research Institute, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea.

Anticancer Research
|June 28, 2003
PubMed
Abstract

Insights

Combined gene therapy using herpes simplex virus thymidine kinase (Tk), GM-CSF, and IL-4 effectively enhances antitumor immunity. This approach boosts dendritic cell (DC) function, leading to suppressed tumor growth and increased survival rates in mice.

Area of Science:

  • Immunology
  • Gene Therapy
  • Oncology

Background:

  • Tumor cells evade immune surveillance through inadequate tumor antigen release and defective dendritic cell (DC) antigen presentation.
  • Understanding these escape mechanisms is crucial for developing effective cancer immunotherapies.

Purpose of the Study:

  • To investigate the efficacy of combined gene therapy using herpes simplex virus thymidine kinase (Tk), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-4 (IL-4) delivered via an adenoviral vector.
  • To address tumor antigen release and DC antigen presentation defects in Lewis lung carcinoma (LLC) models.

Main Methods:

  • Lewis lung carcinoma (LLC) was established in a mouse model.
  • Vaccinations were performed using LLC cells transduced with Tk, GM-CSF, and IL-4, individually and in combination.
  • Tumor growth, survival rates, and DC infiltration in the spleen were assessed.

Main Results:

  • Vaccination with Tk alone or Tk with IL-4 did not suppress wild-type LLC growth.
  • The combination of Tk and GM-CSF delayed tumor growth.
  • The combined Tk-GM-CSF-IL-4 gene therapy markedly suppressed tumor growth and improved mouse survival.
  • Immunohistochemistry revealed dense DC infiltration in the spleen of mice treated with Tk-GM-CSF-IL-4.

Conclusions:

  • Combined gene therapy with Tk-GM-CSF-IL-4 is effective in inducing antitumor immunity.
  • This therapeutic approach enhances DC functions, leading to improved control of tumor growth.
  • The findings suggest a promising strategy for cancer immunotherapy by modulating the tumor microenvironment and immune cell activity.

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