{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:09:52Z","timestamp":1778310592797,"version":"3.51.4"},"reference-count":18,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Mens Health"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Prostate cancer is among the most prevalent malignancies in men worldwide and is associated with poor outcomes in advanced stages. Conventional therapies, including androgen deprivation and chemotherapy, provide limited benefit and are often accompanied by significant toxicity. This study aimed to evaluate the efficacy and immunological impact of a novel bispecific single-chain antibody targeting prostate-specific membrane antigen (PSMA) and CD3 in preclinical models. A bispecific single-chain variable fragment (scFv) antibody was engineered to simultaneously bind PSMA on tumor cells and CD3 on T cells. The construct was expressed in mammalian cell lines, and its purity, specificity, and binding affinity were characterized. In vivo efficacy was assessed in murine xenograft models of prostate cancer, with treatment groups receiving human T cells with or without the bispecific antibody. Tumor growth, survival, and immunological responses were evaluated using flow cytometry, immunohistochemistry, and histopathological analysis. The bispecific antibody demonstrated high purity (mean 97.7%), strong binding affinity to PSMA (Kd 0.23 nM) and CD3 (Kd 0.30 nM), and specificity &gt;99%. In vivo, treatment significantly reduced tumor growth (75.45 \u00b1 3.52 mm\u00b3 vs. 543.39 \u00b1 44.35 mm\u00b3 in controls at Day 28; Student\u2019s\n                    <jats:italic toggle=\"yes\">t<\/jats:italic>\n                    -test, t(28) = 40.52,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; .001) and prolonged survival (59.00 \u00b1 0.84 vs. 31.00 \u00b1 0.84 days; Log-rank test,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; .001). Enhanced T-cell activation, infiltration, and IFN-\u03b3 release were observed, accompanied by increased tumor necrosis and apoptosis. The PSMA-CD3 bispecific antibody effectively redirected T-cell cytotoxicity against prostate cancer cells, resulting in robust antitumor activity and survival benefit. These findings support further translational development of bispecific immunotherapies for advanced prostate cancer.\n                  <\/jats:p>","DOI":"10.1177\/15579883261439951","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T23:43:33Z","timestamp":1778111013000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Evaluation of a Bispecific Single-Chain Antibody Targeting PSMA and CD3 to Enhance T-Cell-Mediated Lysis"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-1399","authenticated-orcid":false,"given":"Mustafa Abdulkareem","family":"Aljaberi","sequence":"first","affiliation":[{"name":"Faculty of Sciences, University of Tunis El Manar, Tunis, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elyes","family":"Chabchoub","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Medicine, University of Sousse, Sousse, Tunisia"},{"name":"Research Laboratory Molecular Medicine Applied to Genetics, Immunology, Oncology and Infections LR23ES06, Faculty of Medicine, University of Sousse, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Bander N. H. Milowsky M. I. Nanus D. M. Kostakoglu L. Vallabhajosula S. Goldsmith S. J. (2005). Phase I trial of 177Lu-labeled J591 a monoclonal antibody to prostate-specific membrane antigen in patients with androgen-independent prostate cancer. Journal of Clinical Oncology 23(19) 4591\u20134601. https:\/\/doi.org\/10.1200\/JCO.2005.05.160","DOI":"10.1200\/JCO.2005.05.160"},{"key":"e_1_3_2_3_1","doi-asserted-by":"crossref","unstructured":"Barsouk A. Padala S. A. Vakiti A. Mohammed A. Saginala K. Thandra K. C. Rawla P. Barsouk A. (2020). Epidemiology staging and management of prostate cancer. Medical Sciences 8(3) 28. https:\/\/doi.org\/10.3390\/medsci8030028","DOI":"10.3390\/medsci8030028"},{"key":"e_1_3_2_4_1","unstructured":"Cheng J. Zhao L. Zhang Y. (2024). Recent advances in bispecific antibodies for prostate cancer immunotherapy. 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Bispecific antibodies for the treatment of B-cell lymphoma: Promises unknowns and opportunities. Blood 141(5) 467\u2013480. https:\/\/doi.org\/10.1182\/blood.2021011994","DOI":"10.1182\/blood.2021011994"},{"key":"e_1_3_2_8_1","doi-asserted-by":"crossref","unstructured":"Heitmann J. S. Pfl\u00fcgler M. Jung G. Salih H. R. (2021). Bispecific antibodies in prostate cancer therapy: Current status and perspectives. Cancers 13(3) 549. https:\/\/doi.org\/10.3390\/cancers13030549","DOI":"10.3390\/cancers13030549"},{"key":"e_1_3_2_9_1","doi-asserted-by":"crossref","unstructured":"Huehls A. M. Coupet T. A. Sentman C. L. (2015). Bispecific T-cell engagers for cancer immunotherapy. Immunology and Cell Biology 93(3) 290\u2013296. https:\/\/doi.org\/10.1038\/icb.2014.93","DOI":"10.1038\/icb.2014.93"},{"key":"e_1_3_2_10_1","doi-asserted-by":"crossref","unstructured":"Hummel H. D. Kufer P. Gr\u00fcllich C. Deschler-Baier B. Chatterjee M. Goebeler M. E. Miller K. de Santis M. Loidl W. Buck A. K. Becht C. Bhore R. Kriner M. Teltschik H. M. Lejeune M. Sherwood M. T. Bargou R. (2021). Pasotuxizumab a BiTE\u00ae immune therapy for metastatic castration-resistant prostate cancer: Phase I dose-escalation study. Immunotherapy 13(2) 125\u2013134. https:\/\/doi.org\/10.2217\/imt-2020-014","DOI":"10.2217\/imt-2020-0256"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00896-6"},{"key":"e_1_3_2_12_1","doi-asserted-by":"crossref","unstructured":"Labrijn A. F. Janmaat M. L. Reichert J. M. Parren P. W. H. I. (2019). Bispecific antibodies: A mechanistic review of the pipeline. Nature Reviews Drug Discovery 18(8) 585\u2013608. https:\/\/doi.org\/10.1038\/s41573-019-0028-1","DOI":"10.1038\/s41573-019-0028-1"},{"key":"e_1_3_2_13_1","unstructured":"Lan T. Chen L. Wei X. (2023). Inflammatory pathways and immune checkpoint inhibitors. Frontiers in Pharmacology 14 Article 1228378. https:\/\/doi.org\/10.3389\/fphar.2023.1228378"},{"issue":"17","key":"e_1_3_2_14_1","first-page":"3629","article-title":"Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium","volume":"57","author":"Liu H.","year":"1997","unstructured":"Liu H., Moy P., Kim S., Xia Y., Rajasekaran A., Navarro V., Knudsen B., Bander N. H. (1997). Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Research, 57(17), 3629\u20133634.","journal-title":"Cancer Research"},{"key":"e_1_3_2_15_1","doi-asserted-by":"crossref","unstructured":"Scher H. I. Fizazi K. Saad F. Taplin M. E. Sternberg C. N. Miller K. de Wit R. Mulders P. Chi K. N. Shore N. D. Armstrong A. J. Flaig T. W. Fl\u00e9chon A. Mainwaring P. Fleming M. Hainsworth J. D. Hirmand M. Selby B. Seely L. de Bono J. S. (2012). Increased survival with enzalutamide in prostate cancer after chemotherapy. New England Journal of Medicine 367(13) 1187\u20131197. https:\/\/doi.org\/10.1056\/NEJMoa1207506","DOI":"10.1056\/NEJMoa1207506"},{"key":"e_1_3_2_16_1","doi-asserted-by":"crossref","unstructured":"Teo M. Y. Rathkopf D. E. Kantoff P. (2019). Treatment of advanced prostate cancer. Annual Review of Medicine 70 479\u2013497. https:\/\/doi.org\/10.1146\/annurev-med-051517-011947","DOI":"10.1146\/annurev-med-051517-011947"},{"key":"e_1_3_2_17_1","doi-asserted-by":"crossref","unstructured":"Virgolini I. Decristoforo C. Haug A. Fanti S. Uprimny C. (2018). Current status of theranostics in prostate cancer. 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Journal of Hematology & Oncology 14(1) Article 59. https:\/\/doi.org\/10.1186\/s13045-021-01065-3"}],"container-title":["American Journal of Men's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15579883261439951","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15579883261439951","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15579883261439951","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T06:18:21Z","timestamp":1778307501000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15579883261439951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1177\/15579883261439951"],"URL":"https:\/\/doi.org\/10.1177\/15579883261439951","relation":{},"ISSN":["1557-9883","1557-9891"],"issn-type":[{"value":"1557-9883","type":"print"},{"value":"1557-9891","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"article-number":"15579883261439951"}}