{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:04:55Z","timestamp":1784613895088,"version":"3.55.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oncolytic virotherapy (OVT) represents a promising approach for cancer treatment, employing oncolytic viruses (OVs) that selectively infect and lyse tumor cells while promoting an antitumor immune microenvironment. Vaccinia virus (VACV) serves as an attractive oncolytic vector due to its favorable safety profile, ease of genetic modification, and inherent tumor selectivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To enhance both safety and tumor-targeting capability, we constructed a recombinant vaccinia virus, VV-dTF\/EE, by deleting the viral\n                      <jats:italic>J2R<\/jats:italic>\n                      and\n                      <jats:italic>F4L<\/jats:italic>\n                      genes and inserting the human neutrophil elastase (ELANE) gene, which exhibits tumor-killing activity. Mechanistic studies evaluated with virus replication selectivity, cell apoptosis, genomic damage, immunogenic cell death, alongside analysis of the immune microenvironment. Efficacy was tested in multiple tumor cell models\n                      <jats:italic>in vitro<\/jats:italic>\n                      and lung cancer models\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In tumor cell lines and mouse tumor models, VV-dTF\/EE demonstrated tumor-restricted replication, potent oncolytic effects, and induction of immunogenic cell death. Furthermore, VV-dTF\/EE augmented VACV-induced antitumor immunity by increasing CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration and suppressing M2-like macrophage polarization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This VV-dTF\/EE revealed tumor-selective replication and killing ability while modifying the tumor immune microenvironment to elicit immunogenic cell death. Our findings highlight a novel strategy for safe and effective tumor immunotherapy through dual-gene deletion and ELANE expression in an oncolytic vaccinia platform.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1861346","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:34:46Z","timestamp":1784612086000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["J2R\/F4L deleted oncolytic vaccinia virus synergizes with tumor specific killer (ELANE) promotes antitumor immunity with superior safety"],"prefix":"10.3389","volume":"17","author":[{"given":"Yu","family":"Huang","sequence":"first","affiliation":[{"name":"Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical 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