Partially circumventing peripheral tolerance for oncogene-specific prostate cancer immunotherapy
dc.contributor.author | Neeley, Yilin C. | en_US |
dc.contributor.author | Arredouani, Mohamed S. | en_US |
dc.contributor.author | Hollenbeck, Brent K. | en_US |
dc.contributor.author | Eng, Marvin H. | en_US |
dc.contributor.author | Rubin, Mark A. | en_US |
dc.contributor.author | Sanda, Martin G. | en_US |
dc.date.accessioned | 2008-05-12T13:36:50Z | |
dc.date.available | 2009-06-01T20:08:52Z | en_US |
dc.date.issued | 2008-05-15 | en_US |
dc.identifier.citation | Neeley, Yilin C.; Arredouani, Mohamed S.; Hollenbeck, Brent; Eng, Marvin H.; Rubin, Mark A.; Sanda, Martin G. (2008). "Partially circumventing peripheral tolerance for oncogene-specific prostate cancer immunotherapy." The Prostate 68(7): 715-727. <http://hdl.handle.net/2027.42/58560> | en_US |
dc.identifier.issn | 0270-4137 | en_US |
dc.identifier.issn | 1097-0045 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/58560 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18302222&dopt=citation | en_US |
dc.description.abstract | BACKGROUND Failure of cancer immunotherapy is essentially due to immunological tolerance to tumor-associated antigens (TAAs), as these antigens are also expressed in healthy tissues. METHODS Here, we used transgenic adenocarcinoma of mouse prostate (TRAMP) mice, which develop lethal prostate cancer due to prostate-specific expression of SV40 T antigen (Tag), to evaluate effects of prostatic transformation on oncogene TAA-specific tolerance and to test the possibility of breaking such tolerance using a modified recombinant vaccinia virus. RESULTS We showed that Tag expression in TRAMP mice is uniquely extra-thymic, and levels of prostatic Tag expression positively correlate with malignant transformation of the prostate. Yet, young tumor-free TRAMP mice were tolerant to Tag antigen. We therefore attempted overcoming such peripheral oncogene-specific T cell tolerance through immunization with a vaccinia construct encoding Tag immunogenic epitopes. This vaccination modality showed that oncogene-specific tolerance was successfully overcome by effective in vivo priming of Tag-specific cytotoxic T cells (CTLs). However, this was restricted to young TRAMP mice. Tag-specific CTL from “tumor naÏve” young TRAMP mice showed significant anti-tumor efficacy in vivo by eliminating established heterotopic prostate tumors and prolonging survival in SCID mice harboring Tag-expressing tumors. In contrast, older TRAMP mice with established prostate tumors exhibited oncogene-specific tolerance as evidenced by failure to generate Tag-specific CTL following Tag-specific immunization. CONCLUSIONS Peripheral tolerance can be overcome for effective anti-tumor therapy following oncogene-specific immunization. However, this ability to elicit oncogene-specific CTL is impeded in the tumor-bearing host, in the context of increased oncogene expression associated with tumor progression. Prostate 68: 715–727, 2008. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 468302 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Partially circumventing peripheral tolerance for oncogene-specific prostate cancer immunotherapy | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Departments of Urology, Surgery, and Pathology, University of Michigan. Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Departments of Urology, Surgery, and Pathology, University of Michigan. Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Departments of Urology, Surgery, and Pathology, University of Michigan. Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Departments of Urology, Surgery, and Pathology, University of Michigan. Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts | en_US |
dc.contributor.affiliationother | Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts ; BIDMC/Division of Urology, Rabb 440, 330 Brookline Ave, Boston, MA 02115. | en_US |
dc.identifier.pmid | 18302222 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/58560/1/20689_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/pros.20689 | en_US |
dc.identifier.source | The Prostate | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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