期刊
PLOS ONE
卷 9, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0093231
关键词
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资金
- National Institutes of Health-National Cancer Institute Early Detection Research Network [UO1-CA113913]
- National Cancer Institute Prostate Specialized Program of Research Excellence Career Development Award [2P50CA90381-06]
- Prostate Cancer Foundation Young Investigator Award
- Prostate Cancer Foundation A. Mazzone Challenge Award
- US Department of Defense Prostate Cancer Research Program New Investigator Award [W81XWH-09-1-0448]
- US Department of Defense Prostate Cancer Research Program Laboratory-Clinical Transition Award [W81XWH-09-1-0156]
- US Department of Defense Prostate Cancer Research Program Laboratory-Postdoctoral Training Award [W81XWH-12-PCRP-PTA]
Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens. Based on our prior genome-wide interrogation of human prostate cancer tissues to identify genes over-expressed in cancer and absent in the periphery, we targeted SIM2 as a prototype autologous tumor antigen for these studies. Using humanized transgenic mice we found that the 9aa HLA-A*0201 epitope, SIM2(237-245), was effective at inducing an antigen specific response against SIM2-expressing prostate cancer cell line, PC3. Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-gamma response in CD8 T cells to the HLA-A*0201-restricted SIM2(237-245) epitope, and an IL-2 response by CD4 T cells to the SIM2(240-254) epitope. This peptide was also effective at inducing CD8(+) T-cells that responded specifically to SIM2-expressing tumor cells. Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers.
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