{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:33:59Z","timestamp":1778924039836,"version":"3.51.4"},"reference-count":9,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors.<\/jats:p><jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> After optimal repeated tumor resection, multiple injections of murine vector\u2014producing cells shedding murine replication\u2014defective retroviral vectors coding the <jats:italic>herpes simplex virus thymidine kinase type 1 (HSV-Tk1)<\/jats:italic> gene were made into the rim of the resection cavity. Fourteen days after the vector-producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed <jats:italic>HSV-Tk1<\/jats:italic> in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2\u201315 years). Treated brain tumors included seven malignant gliomas, two ependymomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings.<\/jats:p><jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector\u2014producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.<\/jats:p>","DOI":"10.3171\/jns.2000.92.2.0249","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:33:09Z","timestamp":1242235989000},"page":"249-254","source":"Crossref","is-referenced-by-count":68,"title":["Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector\u2014producer cells followed by intravenous ganciclovir administration"],"prefix":"10.3171","volume":"92","author":[{"given":"Roger J.","family":"Packer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cory","family":"Raffel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith G.","family":"Villablanca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg-Christian","family":"Tonn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan E.","family":"Burdach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Burger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"LaFond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Gordon","family":"McComb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip H.","family":"Cogen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Vezina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard P.","family":"Kapcala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Cancer Gene Ther","first-page":"S42","article-title":"Phase II trial of GLI 328 HSV-TK gene therapy in recurrent glioblastoma.","volume":"4","author":"Berger","year":"1997"},{"key":"b2","series-title":"Hum Gene Ther","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1089\/hum.1995.6.11-1467","article-title":"Effects of herpes simplex virus thymidine kinase expression levels on ganciclovir-mediated cytotoxicity and the \u201cbystander effect.\u201d","volume":"6","author":"Chen","year":"1995"},{"key":"b3","series-title":"Science","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1126\/science.1317968","article-title":"In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors.","volume":"256","author":"Culver","year":"1992"},{"key":"b4","series-title":"Arch Neurol","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1001\/archneur.56.4.449","article-title":"New molecular strategies to cure brain tumors.","volume":"56","author":"Fathallah-Shaykh","year":"1999"},{"key":"b5","series-title":"Evaluation of Chemotherapeutic Agents.","first-page":"191","article-title":"The clinical evaluation of chemotherapeutic agents in cancer","author":"Karnofsky","year":"1949"},{"key":"b6","series-title":"Hum Gene Ther","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1089\/hum.1998.9.8-1165","article-title":"Biosafety monitoring of patients receiving intracerebral injections of murine retroviral producer cells.","volume":"9","author":"Long","year":"1998"},{"key":"b7","series-title":"Arch Neurol","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1001\/archneur.56.4.421","article-title":"Brain tumors in children.","volume":"56","author":"Packer","year":"1999"},{"key":"b8","series-title":"Nat Med","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1038\/nm1297-1354","article-title":"Therapy of malignant brain tumors by intratumoral implantation of retrovirus vector-producing cells.","volume":"3","author":"Ram","year":"1997"},{"key":"b9","series-title":"J Natl Cancer Inst","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1093\/jnci\/90.17.1269","article-title":"Trends in reported incidence of primary malignant brain tumors in children in the United States.","volume":"90","author":"Smith","year":"1998"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/92\/2\/article-p249.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/92\/2\/article-p249.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/92\/2\/article-p249.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:06:52Z","timestamp":1679893612000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/92\/2\/article-p249.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,2]]},"references-count":9,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3171\/jns.2000.92.2.0249","relation":{},"ISSN":["0022-3085"],"issn-type":[{"value":"0022-3085","type":"print"}],"subject":[],"published":{"date-parts":[[2000,2]]}}}