Androgen ablation augments human HLA2.1-restricted T cell responses to PSA self-antigen in transgenic mice
dc.contributor.author | Arredouani, Mohamed S. | en_US |
dc.contributor.author | Tseng-Rogenski, Stephanie S. | en_US |
dc.contributor.author | Hollenbeck, Brent K. | en_US |
dc.contributor.author | Escara-Wilke, June | en_US |
dc.contributor.author | Leander, Karen R. | en_US |
dc.contributor.author | Defeo-Jones, Deborah | en_US |
dc.contributor.author | Hwang, Clara | en_US |
dc.contributor.author | Sanda, Martin G. | en_US |
dc.date.accessioned | 2010-06-02T19:50:15Z | |
dc.date.available | 2011-03-01T16:26:46Z | en_US |
dc.date.issued | 2010-06-15 | en_US |
dc.identifier.citation | Arredouani, Mohamed S.; Tseng-Rogenski, Stephanie S.; Hollenbeck, Brent K.; Escara-Wilke, June; Leander, Karen R.; Defeo-Jones, Deborah; Hwang, Clara; Sanda, Martin G. (2010). "Androgen ablation augments human HLA2.1-restricted T cell responses to PSA self-antigen in transgenic mice." The Prostate 70(9): 1002-1011. <http://hdl.handle.net/2027.42/75780> | en_US |
dc.identifier.issn | 0270-4137 | en_US |
dc.identifier.issn | 1097-0045 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/75780 | |
dc.description.abstract | BACKGROUND In recent years, there has been an increasing interest in targeting human prostate tumor-associated antigens (TAAs) for prostate cancer immunotherapy as an alternative to other therapeutic modalities. However, immunologic tolerance to TAA poses a significant obstacle to effective, TAA-targeted immunotherapy. We sought to investigate whether androgen deprivation would result in circumventing immune tolerance to prostate TAA by impacting CD8 cell responses. METHODS To this end, we generated a transgenic mouse that expresses the human prostate-specific antigen (PSA) specifically in the prostate, and crossed it to the HLA-A2.1 transgenic mouse to evaluate how androgen deprivation affects human HLA A2.1-resticted T cell responses following immunization of PSA-expressing mice by vaccinia-PSA (PROSTVAC). RESULTS Our PSA transgenic mouse showed restricted expression of PSA in the prostate and detectable circulating PSA levels. Additionally, PSA expression was androgen-dependent with reduced PSA expression in the prostate within 1 week of castration, and undetectable PSA by day 42 after castration as evaluated by ELISA. Castration of the PSA/A2.1 hybrid mouse prior to immunization with a PSA-expressing recombinant vaccinia virus resulted in a significant augmentation of PSA-specific cytotoxic lymphocytes. CONCLUSIONS This humanized hybrid mouse model provides a well-defined system to gain additional insight into the mechanisms of immune tolerance to PSA and to test novel strategies aiming at circumventing immune tolerance to PSA and other TAA for targeted prostate cancer immunotherapy. Prostate © 2010 Wiley-Liss, Inc. | en_US |
dc.format.extent | 306432 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 | Androgen ablation augments human HLA2.1-restricted T cell responses to PSA self-antigen in transgenic mice | 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 | Department of Urology & Department of Microbiology and Immunology, School of Medicine, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Urology & Department of Microbiology and Immunology, School of Medicine, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Urology & Department of Microbiology and Immunology, School of Medicine, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Urology & Department of Microbiology and Immunology, School of Medicine, 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 | Merck Research Laboratories, West Point, Pennsylvania | en_US |
dc.contributor.affiliationother | Merck Research Laboratories, West Point, Pennsylvania | en_US |
dc.contributor.affiliationother | Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts ; 330 Brookline Ave., Rabb 440, Boston, MA 02215. | en_US |
dc.identifier.pmid | 20209643 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/75780/1/21134_ftp.pdf | |
dc.identifier.doi | 10.1002/pros.21134 | en_US |
dc.identifier.source | The Prostate | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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