Immunostimulatory effects of CpG-ODN upon dendritic cell-based immunotherapy in a murine melanoma model.
In this study, we examined the protective and therapeutic efficacy of the immunoadjuvant CpG in combination with dendritic cell (DC) immunotherapy in a murine melanoma model. We found that murine bone-marrow derived DC stimulated in vitro with CpG displayed both enhanced expression of maturation markers and secretion of IL-12p70 and IL-10. In addition, these matured DC demonstrated enhanced ability to stimulate antigen specific CD4+ and CD8+ T cell responses in vitro. In a protection model, C57BL/6 mice vaccinated with either antigen-pulsed immature or CpG matured DC were unable to reject a lethal B16 melanoma challenge. In contrast, long-term protection was achieved in mice vaccinated with both CpG and antigen-pulsed DC, which correlated with an enhanced antigen specific T cell immune response. In a therapeutic model of established subcutaneous B16 melanoma, C57BL/6 mice treated intratumorally with CpG and B16 lysate-pulsed DC demonstrated a reduced tumor burden and prolonged survival. In a similar model of established subcutaneous tumor, mice treated with CpG-matured DC pulsed with a melanoma peptide, TRP-2, alone were unable to achieve tumor regression. Conversely, mice that received the combined vaccine of CpG and peptide-pulsed DC displayed a reduced tumor burden. These experiments provide evidence that combined immunization with both antigen-pulsed DC and the immunoadjuvant, CpG, can lead to tumor regression and long-term survival in a murine B16 melanoma model.
Pilon-Thomas
Shari
S
Division of Cutaneous Oncology and the Immunology and Immunotherapy Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
Li
Wenbin
W
Briggs
Jon J
JJ
Djeu
Julie
J
Mulé
James J
JJ
Riker
Adam I
AI
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000187:drug effects*; D004195:Disease Models, Animal; D016219:Immunotherapy, Adoptive; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D009838:Oligodeoxyribonucleotides