{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:15:08Z","timestamp":1777670108722,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"19-20","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:p>Brain tumors represent the most common pediatric solid neoplasms and leading cause of childhood cancer-related morbidity and mortality. Although most adult brain tumors are supratentorial and arise in the cerebrum, the majority of pediatric brain tumors are infratentorial and arise in the posterior fossa, specifically the cerebellum. Outcomes from malignant cerebellar tumors are unacceptable despite aggressive treatments (surgery, radiation, and\/or chemotherapy) that are harmful to the developing brain. Novel treatments\/approaches such as oncolytic virotherapy are urgently needed. Preclinical and prior clinical studies suggest that genetically engineered oncolytic herpes simplex virus (HSV-1) G207 can safely target cerebellar malignancies and has potential to induce an antitumor immune response at local and distant sites of disease, including spinal metastases and leptomeningeal disease. Herein, we outline the rationale, design, and significance of a first-in-human immunotherapy Phase 1 clinical trial targeting recurrent cerebellar malignancies with HSV G207 combined with a single low-dose of radiation (5 Gy), designed to enhance virus replication and innate and adaptive immune responses. We discuss the unique challenges of inoculating virus through intratumoral catheters into cerebellar tumors. The trial utilizes a single arm open-label traditional 3\u2009+\u20093 design with four dose cohorts. The primary objective is to assess safety and tolerability of G207 with radiation in recurrent\/progressive malignant pediatric cerebellar tumors. After biopsy to prove recurrence\/progression, one to four intratumoral catheters will be placed followed by a controlled-rate infusion of G207 for 6\u2009h followed by the removal of catheters at the bedside. Radiation will be given within 24\u2009h of virus inoculation. Patients will be monitored closely for toxicity and virus shedding. Efficacy will be assessed by measuring radiographic response, performance score, progression-free and overall survival, and quality of life. The data obtained will be invaluable in our efforts to produce more effective and less toxic therapies for children with high-grade brain tumors.<\/jats:p>","DOI":"10.1089\/hum.2020.101","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T02:49:58Z","timestamp":1594608598000},"page":"1132-1139","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":31,"title":["Design and Rationale for First-in-Human Phase 1 Immunovirotherapy Clinical Trial of Oncolytic HSV G207 to Treat Malignant Pediatric Cerebellar Brain Tumors"],"prefix":"10.1177","volume":"31","author":[{"given":"Joshua D.","family":"Bernstock","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asim K.","family":"Bag","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, Tennessee, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Fiveash","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara","family":"Kachurak","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galal","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Chagoya","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Gessler","sequence":"additional","affiliation":[{"name":"Department for Neurosurgery, Goethe University Frankfurt, Frankfurt am Main, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo A.","family":"Valdes","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avi","family":"Madan-Swain","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Whitley","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Disease, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Markert","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Yancey","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory K.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA."},{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3171\/2018.10.PEDS18377"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000545"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.1953"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/mto.2015.15"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/mto.2015.16"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301205"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.228"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.22"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2017.002"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2173860"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0995-938"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.8.6319-6326.1999"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.8.3832-3841.2000"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300546"},{"key":"e_1_3_4_16_2","first-page":"1517","article-title":"Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus","volume":"5","author":"Bradley JD","year":"1999","unstructured":"Bradley JD, , Kataoka Y, , Advani S, et al. Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus. Clin Cancer Res, 1999; 5:1517\u20131522.","journal-title":"Clin Cancer Res"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.61"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21358"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-009-9926-0"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3010298"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32353-x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nov123"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-019-0091-0"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.11.122"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1678921"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.7.8.6216"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/mto.2014.10"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950018832"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-017-0516-0"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-016-2151-8"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25277"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.12.061"},{"key":"e_1_3_4_33_2","first-page":"i100","article-title":"IMMU-08. Phase I Trial (NCT02457845) safety, tolerability and preliminary efficacy of immunovirotherapy with HSV G207 in children with progressive malignant supratentorial brain tumors","volume":"20","author":"Friedman G","year":"2018","unstructured":"Friedman G, , Bag A, , Madan-Swain A, et al. IMMU-08. Phase I Trial (NCT02457845) safety, tolerability and preliminary efficacy of immunovirotherapy with HSV G207 in children with progressive malignant supratentorial brain tumors. Neurooncology, 2018; 20:i100.","journal-title":"Neurooncology"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2007-016"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2009.09.005"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1177\/088307389501000304"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","unstructured":"Neville KA Blaney SM. Leptomeningeal cancer in the pediatric patient. 2005:87\u2013106.","DOI":"10.1007\/0-387-24199-X_6"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-013-1213-4"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00236-3"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.3377"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-016-5286-0"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2020.101","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2020.101","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2020.101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:55:20Z","timestamp":1777449320000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2020.101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":40,"journal-issue":{"issue":"19-20","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1089\/hum.2020.101"],"URL":"https:\/\/doi.org\/10.1089\/hum.2020.101","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}