Application of Apoptogenic Pretreatment to Enhance Anti-tumor Immunity of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)-secreting CT26 Tumor Cells.
- Author:
Do Youn JUN
1
;
Elizabeth M JAFFEE
;
Young Ho KIM
Author Information
- Publication Type:Original Article
- Keywords: CT26 tumor; GM-CSF; apoptotic pretreatment; cancer vaccine; anti-tumor immune response
- MeSH: Animals; Apoptosis; Colony-Stimulating Factors*; Colorectal Neoplasms; Granulocyte-Macrophage Colony-Stimulating Factor; Mice; Mitomycin; Vaccination; Vaccines; Zidovudine
- From:Immune Network 2005;5(2):110-116
- CountryRepublic of Korea
- Language:English
- 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.
