Immune Netw.
2005 Jun;5(2):110-116. 10.4110/in.2005.5.2.110.
Application of Apoptogenic Pretreatment to Enhance Anti-tumor Immunity of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)-secreting CT26 Tumor Cells
- Affiliations
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- 1Institute of Genetic Engineering, Kyungpook National University, Daegu, Korea.
- 2Division of Immunology and Hematopoiesis, The Sidney Kimmel Comprehensive Center at Johns Hopkins, Baltimore, Maryland, USA.
- 3Laboratory of Immunobiology, Department of Microbiology, College of Natural Sciences, Kyungpook National University, Daegu, Korea. ykim@knu.ac.kr
- KMID: 2150605
- DOI: http://doi.org/10.4110/in.2005.5.2.110
Abstract
- BACKGROUND
As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. METHODS: A carcinogen- induced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with gamma-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. RESULTS: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with gamma-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. CONCLUSION: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by gamma-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.
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