BACKGROUND: 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. METHODS: 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 gamma (IFN-gamma) 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. RESULTS: Among 10 samples of advanced colorectal carcinoma, 6 samples (60%) overexpressed EphA2. IFN-gamma 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. CONCLUSIONS: The current results demonstrated that Eph-DC vaccines may represent a promising preventative/therapeutic modality in the cancer setting.
BACKGROUND: 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 murinecolon cancer model. METHODS: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 gamma (IFN-gamma) 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 murinecolorectal adenocarcinoma (MC38) mousecolon 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. RESULTS: Among 10 samples of advanced colorectal carcinoma, 6 samples (60%) overexpressed EphA2. IFN-gamma 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. CONCLUSIONS: The current results demonstrated that Eph-DC vaccines may represent a promising preventative/therapeutic modality in the cancer setting.
Authors: Xi Zhao; Anamika Bose; Hideo Komita; Jennifer L Taylor; Nina Chi; Devin B Lowe; Hideho Okada; Ying Cao; Debabrata Mukhopadhyay; Peter A Cohen; Walter J Storkus Journal: J Immunol Date: 2012-01-13 Impact factor: 5.422
Authors: Aparna Rao; Jennifer L Taylor; Nina Chi-Sabins; Mayumi Kawabe; William E Gooding; Walter J Storkus Journal: Cancer Res Date: 2012-05-02 Impact factor: 12.701
Authors: Benchun Miao; Zhenyu Ji; Li Tan; Michael Taylor; Jianming Zhang; Hwan Geun Choi; Dennie T Frederick; Raj Kumar; Jennifer A Wargo; Keith T Flaherty; Nathanael S Gray; Hensin Tsao Journal: Cancer Discov Date: 2014-12-26 Impact factor: 39.397
Authors: Mayumi Kawabe; Maja Mandic; Jennifer L Taylor; Cecilia A Vasquez; Amy K Wesa; Leonard M Neckers; Walter J Storkus Journal: Cancer Res Date: 2009-08-18 Impact factor: 12.701
Authors: Amy K Wesa; Christopher J Herrem; Maja Mandic; Jennifer L Taylor; Cecilia Vasquez; Mayumi Kawabe; Tomohide Tatsumi; Michael S Leibowitz; James H Finke; Ronald M Bukowski; Elizabeth Bruckheimer; Michael S Kinch; Walter J Storkus Journal: J Immunol Date: 2008-12-01 Impact factor: 5.422