{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:43:34Z","timestamp":1793119414542,"version":"4.5.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National institute of Health, USA","award":["NIH-R21-CA252010"],"award-info":[{"award-number":["NIH-R21-CA252010"]}]},{"name":"National Institute of Health, USA","award":["NIH-R01-CA218596"],"award-info":[{"award-number":["NIH-R01-CA218596"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD\/<jats:italic>mut<\/jats:italic>TK<jats:sub>SR39<\/jats:sub><jats:italic>rep<\/jats:italic>-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 \u00d7 10<jats:sup>10<\/jats:sup>, to 1 \u00d7 10<jats:sup>12<\/jats:sup> viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFN\u03b3, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 10<jats:sup>12<\/jats:sup> viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1\/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFN\u03b3, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD\/<jats:italic>mut<\/jats:italic>TK<jats:sub>SR39<\/jats:sub><jats:italic>rep<\/jats:italic>-hIL-12) was well tolerated when administered locally to prostate tumors.<\/jats:p>","DOI":"10.1371\/journal.pone.0291315","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T17:24:09Z","timestamp":1694798649000},"page":"e0291315","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate 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