The first two authors contributed equally to this article.
Immunotherapy of murine colon cancer using receptor tyrosine kinase EphA2-derived peptide-pulsed dendritic cell vaccines
Article first published online: 8 AUG 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 7, pages 1469–1477, 1 October 2007
How to Cite
Yamaguchi, S., Tatsumi, T., Takehara, T., Sakamori, R., Uemura, A., Mizushima, T., Ohkawa, K., Storkus, W. J. and Hayashi, N. (2007), Immunotherapy of murine colon cancer using receptor tyrosine kinase EphA2-derived peptide-pulsed dendritic cell vaccines. Cancer, 110: 1469–1477. doi: 10.1002/cncr.22958
- Issue published online: 14 SEP 2007
- Article first published online: 8 AUG 2007
- Manuscript Accepted: 6 JUN 2007
- Manuscript Revised: 8 MAY 2007
- Manuscript Received: 9 JAN 2007
- Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Grant-in-Aid for Research on Hepatitis and Bovine Spongiform Encephalopathy from the Ministry of Health, Labor, and Welfare of Japan
- dendritic cells;
- colorectal cancer;
- cancer immunotherapy
Further optimization of dendritic cell (DC)-based vaccines is required clinically against advanced stage cancer. Given the broad range of expression levels observed in the recently defined tumor antigen EphA2 in a diverse types of cancers, especially in advanced stage or metastatic cancers, the authors evaluated the effectiveness of vaccination using DCs pulsed with EphA2-derived peptides (Eph-DCs) in a murine colon cancer model.
EphA2 protein expression levels were evaluated in advanced colorectal carcinoma tissues from 10 patients by Western blot analysis. C57BL/6 mice were immunized with Eph-DCs twice weekly. Interferon γ (IFN-γ) ELISPOT assays were used for the analysis of CD8-positive T cells that were specific for EphA2-derived peptide. Immunized mice were challenged subcutaneously with EphA2-positive murine colorectal adenocarcinoma (MC38) mouse colon tumors or with EphA2-negative BL6 melanoma tumors. In some experiments, mice were injected with anti-CD8, anti-CD4, or antiasialo GM1 antibody to deplete corresponding lymphocyte subsets.
Among 10 samples of advanced colorectal carcinoma, 6 samples (60%) overexpressed EphA2. IFN-γ ELISPOT assays revealed that EphA2-derived peptide-specific CD8-positive T cells were generated by immunization with Eph-DCs. Immunization with Eph-DCs inhibited MC38 tumor growth compared with immunization using unpulsed DCs or phosphate-buffered saline. In contrast, Eph-DC vaccination had no effect on BL6 growth. Antibody depletion studies revealed that both CD8-positive T cells and CD4-positive T cells, but not natural killer cells, played critical roles in the efficacy observed for immunizations with Eph-DCs. Eph-DC vaccines resulted in long-term antitumor immunity against a rechallenge with MC38 tumor cells.
The current results demonstrated that Eph-DC vaccines may represent a promising preventative/therapeutic modality in the cancer setting. Cancer 2007. © 2007 American Cancer Society.