{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:21:46Z","timestamp":1792279306000,"version":"4.4.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"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><jats:title>Background<\/jats:title><jats:p>Triple-negative breast cancer (TNBC) is clinically aggressive. CF33-hNIS-antiPDL1, an oncolytic orthopoxvirus, shows robust anti-cancer activity in TNBC xenografts in mice. CF33-hNIS-antiPDL1-infected tumor cells express functional human sodium iodide symporter (hNIS) and are visible by single-photon emission computed tomography (SPECT) or positron emission tomography (PET). We evaluated the ability of virus-encoded hNIS to track OV in mice using PET imaging and in a phase I study in TNBC patients using SPECT. The aim of this first-in-human study was to determine imageability and safety of intratumoral (IT) CF33-hNIS-antiPDL1 injections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Imageability of CF33-hNIS-antiPDL1 was first assessed in mice bearing human xenografts. Virus or PBS-treated mice were imaged using a PET scanner. For the first-in-human trial, 9 patients were enrolled in this phase I, single-center, single-arm trial from October 2021 to August 2023. Key eligibility criteria included unresectable\/metastatic TNBC; progressed on at least 2 prior chemotherapies; ECOG 0-2; RECIST 1.1 measurable disease; and at least one tumor amenable to repeated IT injections. Eligible patients received CF33-hNIS-antiPDL1 IT at 1 of 6 assigned dose levels (ranging from 1 \u00d7 105 PFU to 3 x 108 PFU) on days 1 and 15 of each 28-day cycle for 3 treatment cycles. SPECT whole-body imaging was performed using technetium-99 at cycle 1 day 8.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All mice treated with the virus showed clear PET signal from tumors whereas no signal was observed in PBS-treated mice. In the phase I study, 7 of 9 patients (78%) showed uptake at the injection site on SPECT imaging at C1D8. Five of 5 patients (100%) with injection sites at metastatic subcutaneous nodules, intramuscular masses, or axillary lymph nodes, and 2\/4 patients (50%) with injection sites at matted dermal metastatic lesions had uptake at injected lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SPECT imaging successfully showed enhancement at the injected lesions in 78% of patients treated with CF33-hNIS-antiPDL1, even at low doses of the oncolytic virus (OV), suggesting local viral replication and hNIS expression. This is the first report of hNIS-based imaging to track oncolytic poxvirus replication in humans. This technology holds promise for noninvasive tracking of systemically administered OVs and other therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>https:\/\/www.clinicaltrials.gov\/study\/NCT05081492<\/jats:uri>, identifier NCT05081492.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1565244","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:58:03Z","timestamp":1756191483000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["hNIS-based imaging to monitor treatment with the novel oncolytic virus CF33-hNIS-antiPDL1 in humans with advanced triple negative breast cancer"],"prefix":"10.3389","volume":"15","author":[{"given":"Jamie","family":"Rand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyambabu","family":"Chaurasiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Seiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Meisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuman","family":"Fong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"B1","unstructured":"International 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