{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:20:47Z","timestamp":1770268847286,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,3,5]],"date-time":"2010-03-05T00:00:00Z","timestamp":1267747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["P50 DK065313-1"],"award-info":[{"award-number":["P50 DK065313-1"]}]},{"name":"NIH","award":["R01 CA8241901-A1"],"award-info":[{"award-number":["R01 CA8241901-A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2010,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>In recent years, there has been an increasing interest in targeting human prostate tumor\u2010associated 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\u2010targeted immunotherapy. We sought to investigate whether androgen deprivation would result in circumventing immune tolerance to prostate TAA by impacting CD8 cell responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>To this end, we generated a transgenic mouse that expresses the human prostate\u2010specific antigen (PSA) specifically in the prostate, and crossed it to the HLA\u2010A2.1 transgenic mouse to evaluate how androgen deprivation affects human HLA A2.1\u2010resticted T cell responses following immunization of PSA\u2010expressing mice by vaccinia\u2010PSA (PROSTVAC).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Our PSA transgenic mouse showed restricted expression of PSA in the prostate and detectable circulating PSA levels. Additionally, PSA expression was androgen\u2010dependent 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\u2010expressing recombinant vaccinia virus resulted in a significant augmentation of PSA\u2010specific cytotoxic lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>This humanized hybrid mouse model provides a well\u2010defined 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 \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.21134","type":"journal-article","created":{"date-parts":[[2010,3,5]],"date-time":"2010-03-05T20:52:39Z","timestamp":1267822359000},"page":"1002-1011","source":"Crossref","is-referenced-by-count":25,"title":["Androgen ablation augments human HLA2.1\u2010restricted T cell responses to PSA self\u2010antigen in transgenic mice"],"prefix":"10.1002","volume":"70","author":[{"given":"Mohamed S.","family":"Arredouani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie S.","family":"Tseng\u2010Rogenski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent K.","family":"Hollenbeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"June","family":"Escara\u2010Wilke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen R.","family":"Leander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Defeo\u2010Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin G.","family":"Sanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,3,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpuro0079"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.10276"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20539"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2004.04922.x"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.5252"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00139.x"},{"key":"e_1_2_1_8_2","first-page":"5160","article-title":"Induction of immunity to prostate cancer antigens: Results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte\u2010macrophage colony\u2010stimulating factor using ex vivo gene transfer","volume":"59","author":"Simons JW","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602019"},{"key":"e_1_2_1_10_2","first-page":"1632","article-title":"A phase I trial of a recombinant vaccinia virus expressing prostate\u2010specific antigen in advanced prostate cancer","volume":"6","author":"Eder JP","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.0597"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.08.083"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(98)00539-1"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.01.027"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20906"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(99)00297-6"},{"key":"e_1_2_1_17_2","first-page":"391","article-title":"The role of androgen in the regulation of programmed cell death\/apoptosis in normal and malignant prostatic tissue","volume":"5","author":"Isaacs JT","year":"1994","journal-title":"Semin Cancer Biol"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/35094009"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251140998"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.15.8099"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.6098"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526128"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63112-4"},{"key":"e_1_2_1_24_2","first-page":"41","article-title":"Identification and characterization of a human agonist cytotoxic T\u2010lymphocyte epitope of human prostate\u2010specific antigen","volume":"8","author":"Terasawa H","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1139"},{"key":"e_1_2_1_26_2","doi-asserted-by":"crossref","first-page":"6665","DOI":"10.1128\/jvi.69.11.6665-6677.1995","article-title":"Hierarchy among multiple H\u20102b\u2010restricted cytotoxic T\u2010lymphocyte epitopes within simian virus 40 T antigen","volume":"69","author":"Mylin LM","year":"1995","journal-title":"J Virol"},{"key":"e_1_2_1_27_2","first-page":"17","article-title":"A safety\u2010modified SV40 Tag developed for human cancer immunotherapy","volume":"2","author":"Tseng\u2010Rogenski SS","year":"2008","journal-title":"Drug Des Dev Ther"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-008-0471-z"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.2.169"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3439"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910630215"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.8.2.230"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1593\/neo.07822"},{"key":"e_1_2_1_34_2","article-title":"ETS genetic rearrangements are progression events in prostate tumorigenesis","volume":"457","author":"Carver BS","year":"2009","journal-title":"Nature"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201736"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.4.293"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-003-0451-2"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2059"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214364"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-005-0687-0"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20135"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00274-08"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.7.8.1245"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.21134","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.21134","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.21134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T01:09:08Z","timestamp":1700615348000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.21134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,5]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2010,6,15]]}},"alternative-id":["10.1002\/pros.21134"],"URL":"https:\/\/doi.org\/10.1002\/pros.21134","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,5]]}}}