دورية أكاديمية
Safety and Efficacy of Intraventricular Immunovirotherapy with Oncolytic HSV-1 for CNS Cancers.
| العنوان: | Safety and Efficacy of Intraventricular Immunovirotherapy with Oncolytic HSV-1 for CNS Cancers. |
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| المؤلفون: | Kang KD; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama., Bernstock JD; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama.; Department of Neurosurgery, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts., Totsch SK; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama., Gary SE; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama.; Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, Alabama., Rocco A; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama., Nan L; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama., Li R; Department of Pathology, Children's of Alabama, Birmingham, Alabama., Etminan T; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama., Han X; Department of Neurology, Division of Neuro-Oncology, University of Alabama at Birmingham, Birmingham, Alabama., Beierle EA; Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama., Eisemann T; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California., Wechsler-Reya RJ; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California., Bae S; Department of Medicine, Division of Preventative Medicine, University of Alabama at Birmingham, Birmingham, Alabama., Whitley R; Department of Pediatrics, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama., Gillespie GY; Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama., Markert JM; Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama., Friedman GK; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama.; Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Dec 15; Vol. 28 (24), pp. 5419-5430. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Herpesvirus 1, Human*/genetics , Oncolytic Viruses*/genetics , Oncolytic Virotherapy*/adverse effects , Oncolytic Virotherapy*/methods , Brain Neoplasms*/pathology, Mice ; Animals ; Cell Line, Tumor ; Mice, Inbred CBA ; Poly I |
| مستخلص: | Purpose: Oncolytic virotherapy with herpes simplex virus-1 (HSV) has shown promise for the treatment of pediatric and adult brain tumors; however, completed and ongoing clinical trials have utilized intratumoral/peritumoral oncolytic HSV (oHSV) inoculation due to intraventricular/intrathecal toxicity concerns. Intratumoral delivery requires an invasive neurosurgical procedure, limits repeat injections, and precludes direct targeting of metastatic and leptomeningeal disease. To address these limitations, we determined causes of toxicity from intraventricular oHSV and established methods for mitigating toxicity to treat disseminated brain tumors in mice. Experimental Design: HSV-sensitive CBA/J mice received intraventricular vehicle, inactivated oHSV, or treatment doses (1×107 plaque-forming units) of oHSV, and toxicity was assessed by weight loss and IHC. Protective strategies to reduce oHSV toxicity, including intraventricular low-dose oHSV or interferon inducer polyinosinic-polycytidylic acid (poly I:C) prior to oHSV treatment dose, were evaluated and then utilized to assess intraventricular oHSV treatment of multiple models of disseminated CNS disease. Results: A standard treatment dose of intraventricular oHSV damaged ependymal cells via virus replication and induction of CD8+ T cells, whereas vehicle or inactivated virus resulted in no toxicity. Subsequent doses of intraventricular oHSV caused little additional toxicity. Interferon induction with phosphorylation of eukaryotic initiation factor-2α (eIF2α) via intraventricular pretreatment with low-dose oHSV or poly I:C mitigated ependyma toxicity. This approach enabled the safe delivery of multiple treatment doses of clinically relevant oHSV G207 and prolonged survival in disseminated brain tumor models. Conclusions: Toxicity from intraventricular oHSV can be mitigated, resulting in therapeutic benefit. These data support the clinical translation of intraventricular G207. (©2022 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | P30 AI027767 United States AI NIAID NIH HHS; R01 FD006368 United States FD FDA HHS; P30 AR048311 United States AR NIAMS NIH HHS; P30 CA013148 United States CA NCI NIH HHS; R01 FD005379 United States FD FDA HHS |
| المشرفين على المادة: | 25249-22-3 (Poly I) |
| تواريخ الأحداث: | Date Created: 20221014 Date Completed: 20221216 Latest Revision: 20230616 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9771977 |
| DOI: | 10.1158/1078-0432.CCR-22-1382 |
| PMID: | 36239623 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-22-1382 |