{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:14:10Z","timestamp":1770963250099,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>With aging male populations, the incidence of prostate cancer is increasing globally. Patients with low- to intermediate-risk disease (Gleason score \u22647) are often managed with close surveillance rather than immediate curative intervention; however, progression in a subset of these individuals narrows the window for effective treatment. Minimally invasive, image-guided local therapy enabling early intervention could prevent disease progression and improve progression-free outcomes. To address this unmet need, we evaluated KLS-3021, a novel oncolytic vaccinia virus encoding PH-20, IL-12, and soluble PD1-Fc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>KLS-3021 was assessed in two orthotopic prostate cancer models: a prostate-confined model with bioluminescence-positive, non-gross tumors, and a visible\/palpable locally invasive model with regional lymphatic spread. Mice were randomized to receive vehicle, docetaxel, or KLS-3021, administered on day 9 (prostate-confined) or day 29 (visible\/locally invasive) after implantation of luciferase-labeled PC-3 cells. Tumor growth was tracked longitudinally by bioluminescence imaging, and histopathological analyses were conducted at predefined time points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A single intratumoral injection of KLS-3021 induced profound and durable tumor therapeutic or suppressive efficacy superior to that of docetaxel in prostate-confined or locally invasive diseases. Mechanistic analyses revealed extracellular matrix degradation, enhanced viral spread, increased immune cell infiltration, M1 macrophage polarization, and features of immunogenic cell death in KLS-3021-treated tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results collectively demonstrate the translational potential of KLS-3021 as a minimally invasive or neoadjuvant therapeutic strategy for prostate cancer, especially in patients for whom early, localized intervention is medically feasible.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1765625","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:22:33Z","timestamp":1770960153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["KLS-3021, a multifunctional oncolytic virus, demonstrates potent early-intervention efficacy in preclinical models of prostate-confined and locally advanced prostate 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