{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:30:36Z","timestamp":1790508636961,"version":"4.1.0"},"reference-count":53,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The Cancer Institute of New Jersey","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100030894","name":"Rutgers School of Graduate Studies","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100030894","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dodge Jones Foundation-Abilene","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"TTUHSC School of Pharmacy","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"NIH","award":["R01 CA160762"],"award-info":[{"award-number":["R01 CA160762"]}]},{"name":"NIH","award":["R01 NS032677"],"award-info":[{"award-number":["R01 NS032677"]}]},{"name":"DOD","award":["W81XWH-20-1-0702"],"award-info":[{"award-number":["W81XWH-20-1-0702"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,3,1]]},"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Glioblastoma (GBM), a highly immunosuppressive and often fatal primary brain tumor, lacks effective treatment options. GBMs contain a subpopulation of GBM stem-like cells (GSCs) that play a central role in tumor initiation, progression, and treatment resistance. Oncolytic viruses, especially oncolytic herpes simplex virus (oHSV), replicate selectively in cancer cells and trigger antitumor immunity\u2014a phenomenon termed the \u201cin situ vaccine\u201d effect. Although talimogene laherparepvec (T-VEC), an oHSV armed with granulocyte macrophage-colony stimulating factor (GM-CSF), is Food and Drug Administration (FDA)-approved for melanoma, its use in patients with GBM has not been reported. Interleukin 2 (IL-2) is another established immunotherapy that stimulates T cell growth and orchestrates antitumor responses. IL-2 is FDA-approved for melanoma and renal cell carcinoma but has not been widely evaluated in GBM, and IL-2 treatment is limited by its short half-life, minimal tumor accumulation, and significant systemic toxicity. We hypothesize that local intratumoral expression of IL-2 by an oHSV would avoid the systemic IL-2-related therapeutic drawbacks while simultaneously producing beneficial antitumor immunity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We developed G47\u0394-mIL2 (an oHSV expressing IL-2) using the flip-flop HSV BAC system to deliver IL-2 locally within the tumor microenvironment (TME). We then tested its efficacy in orthotopic mouse GBM models (005 GSC, CT-2A, and GL261) and evaluated immune profiles in the treated tumors and spleens by flow cytometry and immunohistochemistry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>G47\u0394-mIL2 significantly prolonged median survival without any observable systemic IL-2-related toxicity in the 005 and CT-2A models but not in the GL261 model due to the non-permissive nature of GL261 cells to HSV infection. The therapeutic activity of G47\u0394-mIL2 in the 005 GBM model was associated with increased intratumoral infiltration of CD8<jats:sup>+<\/jats:sup> T cells, critically dependent on the release of IL-2 within the TME, and CD4<jats:sup>+<\/jats:sup> T cells as their depletion completely abrogated therapeutic efficacy. The use of anti-PD-1 immune checkpoint blockade did not improve the therapeutic outcome of G47\u0394-mIL2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings illustrate that G47\u0394-mIL2 is efficacious, stimulates antitumor immunity against orthotopic GBM, and may also target GSC. OHSV expressing IL-2 may represent an agent that merits further exploration in patients with GBM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-008880","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T23:35:50Z","timestamp":1712705750000},"page":"e008880","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["Oncolytic herpes simplex virus expressing IL-2 controls glioblastoma growth and improves survival"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-8693","authenticated-orcid":false,"given":"Praveen K","family":"Bommareddy","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Brain Tumor Research Center, Boston, Massachusetts, USA"},{"name":"Cancer Institute of New Jersey (CINJ), New Brunswick, New Jersey, 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