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KMID : 1148920100440030199
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Nuclear Medicine and Molecular Imaging
2010 Volume.44 No. 3 p.199 ~ p.206
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CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy
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Jeon Yong-Hyun
Choi Yun
Lee Jae-Tae
Kim Chul-Woo
Chung June-Key
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Abstract
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Purpose: The authors evaluated whether the cytotoxicity of CD8+CTLs generated by combined hMUC1 vaccination and hNIS radioiodine gene therapy was enhanced in the presence of CpG in an established tumor model.
Methods: CMNF cells (CT26 cells expressing hMUC1, hNIS and Firefly luciferase) were transplanted into BALB/c mice. Four and 10 days later, tumor-bearing mice were immunized intramuscularly with pcDNA3.1 or pcDNA-hMUC1 or pcDNA-hMUC1+CpG, and subsequently administered PBS or 131I [five groups (seven mice/group): referred to as the pcDNA3.1+PBS, phMUC1+PBS, pcDNA3.1+131I, phMUC1+131I, and phMUC1+131I+CpG groups]. The number of CD8+IFNr+ T cells of splenocytes as well as the number of CD8+IFNr+ T cells of splenocytes re-stimulated with CD11c+ cells was determined using FACS analysis. The activities of cytotoxic T cells (CTLs) from splenocytes were investigated.
Results: Marked tumor growth inhibition was observed in the phMUC1+131I and phMUC1+131I+CpG groups, but not in the other three single therapy groups. Particularly the number of CD8+IFN-γ+ T cells of splenocytes was more increased in the phMUC1+131I+CpG group than in the phMUC1+131I group. The number of CD8+IFN-γ+ T cells of splenocytes stimulated with CD11c+ cells was the most enhanced in the phMUC1+131I+CpG group among the five groups. Concurrently, the activities of hMUC1-associated CTLs obtained from splenocytes in the phMUC1+131I+CpG group were significantly greater than in the other four groups (pcDNA+PBS, phMUC1+PBS, pcDNA+131I, phMUC1+131I, and phMUC1+131I+CpG, 16?±?2%, 20?±?1%, 30?±?2%, 60?±?2%, and 87?±?2%, respectively, P?
Conclusion: Our data suggest that adjuvant CpG ODNs can increase the killing activities of CTLs generated by combined hMUC1 DNA vaccination and hNIS radioiodine gene therapy.
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KEYWORD
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CpG oligodeoxynucleotides, hMUC1 vaccination, hNIS radioiodine gene therapy
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