CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy.

Abstract

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 (131)I [five groups (seven mice/group): referred to as the pcDNA3.1+PBS, phMUC1+PBS, pcDNA3.1+(131)I, phMUC1+(131)I, and phMUC1+(131)I+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+(131)I and phMUC1+(131)I+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+(131)I+CpG group than in the phMUC1+(131)I group. The number of CD8+IFN-γ+ T cells of splenocytes stimulated with CD11c+ cells was the most enhanced in the phMUC1+(131)I+CpG group among the five groups. Concurrently, the activities of hMUC1-associated CTLs obtained from splenocytes in the phMUC1+(131)I+CpG group were significantly greater than in the other four groups (pcDNA+PBS, phMUC1+PBS, pcDNA+(131)I, phMUC1+(131)I, and phMUC1+(131)I+CpG, 16 ± 2%, 20 ± 1%, 30 ± 2%, 60 ± 2%, and 87 ± 2%, respectively, P < 0.01).

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.

• Authors: Yong Hyun Jeon, Yun Choi, Jaetae Lee, Chul Woo Kim, June-Key Chung
• Journal: Nuclear medicine and molecular imaging (Nucl Med Mol Imaging) Vol. 44 Issue 3 Pg. 199-206 (Sep 2010) ISSN: 1869-3474 [Print] Germany
• PMID: 24899950 (Publication Type: Journal Article)