Biodistribution, shedding, and transmissibility of vusolimogene oderparepvec (RP1)

作者：Trisha M. Wise-Draper, Caroline Robert, Michael K. Wong, Mark R. Middleton, Joseph J. Sacco, Gino K. In, Eva Muñoz‐Couselo, Dirk Schadendorf, Georgia M. Beasley, Jiaxin Niu, Bartosz Chmielowski, Mohammed Milhem, Tawnya L. Bowles, Katy K. Tsai, Adel Samson, Kevin J. Harrington, Célèste Lebbé, Caroline Gaudy‐Marqueste, Junhong Zhu, Bhavna Paratala, Jeannie W. Hou, Kostas Xynos, Aaron Clack, Robert S. Coffin, Praveen K. Bommareddy · 发表于：Frontiers in Oncology · 年份：2026 · DOI：10.3389/fonc.2026.1798502 · 研究领域：Virus-based gene therapy research、Herpesvirus Infections and Treatments、Polyomavirus and related diseases

Background Vusolimogene oderparepvec (RP1) is an intratumorally administered, genetically modified herpes simplex virus type-1 derived oncolytic immunotherapy designed to selectively replicate in tumors and stimulate systemic antitumor immunity. We evaluated the biodistribution, shedding, and potential for transmission of RP1 in patients with skin cancers treated in the IGNYTE clinical trial and assessed close-contact exposure across all RP1 clinical studies. Methods Patients received intratumoral RP1 in combination with nivolumab, with serial collection of blood, urine, injection-site, dressing, and oral mucosal samples during treatment and follow-up. RP1 DNA was quantified by polymerase chain reaction, and swab samples positive for RP1 DNA were tested for replication-competent RP1. Reports of herpetic infection in patients and close contacts were also systematically collected. Results Among 282 treated patients, RP1 DNA was detected most frequently at injection sites, with substantially lower incidence and levels in other sample types. Detection declined rapidly after treatment completion, with no RP1 DNA detected in blood or urine during follow-up. Replication-competent RP1 was detected rarely and only at low titers, only at injection sites. No systemic herpes simplex virus infections occurred in patients, and no herpetic infections were reported among caregivers or close contacts. Interpretation RP1 is largely confined to injection sites, shedding of live RP1 is rare and ...