دورية أكاديمية
Impact of preimmunization on adenoviral vector expression and toxicity in a subcutaneous mouse cancer model.
| العنوان: | Impact of preimmunization on adenoviral vector expression and toxicity in a subcutaneous mouse cancer model. |
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| المؤلفون: | Vlachaki MT; Department of Radiology, Baylor College of Medicine, Houston, Texas 77030, USA., Hernandez-Garcia A, Ittmann M, Chhikara M, Aguilar LK, Zhu X, Teh BS, Butler EB, Woo S, Thompson TC, Barrera-Saldana H, Aguilar-Cordova E |
| المصدر: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2002 Sep; Vol. 6 (3), pp. 342-8. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print Cited Medium: Print ISSN: 1525-0016 (Print) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : Cambridge, MA : Cell Press Original Publication: San Diego, CA : Academic Press, 2000- |
| مواضيع طبية MeSH: | Genetic Therapy* , Vaccination* , Viral Vaccines*/administration & dosage , Viral Vaccines*/immunology, Dependovirus/*genetics , Genetic Vectors/*immunology , Mammary Neoplasms, Experimental/*therapy, Animals ; Dependovirus/drug effects ; Dependovirus/immunology ; Dependovirus/pathogenicity ; Genes, Reporter ; Genetic Vectors/administration & dosage ; Genetic Vectors/drug effects ; Genetic Vectors/pharmacology ; Genetic Vectors/toxicity ; Hepatitis/pathology ; Immunity ; Liver/drug effects ; Liver/enzymology ; Liver/pathology ; Mammary Neoplasms, Experimental/immunology ; Mice |
| مستخلص: | Immune responses against adenoviral vectors may influence the toxicity and therapeutic effectiveness of adenovirus-mediated gene transfer and may be a limiting factor in adenovirus-mediated gene therapy. The purpose of this study was to determine the effects of preimmunization on intratumoral adenoviral transduction and systemic spread. The hypothesis was that increased doses of adenoviral vectors could overcome local neutralization without added systemic toxicity. The level and duration of gene expression were assessed as a function of time and dose after intratumoral delivery of adenoviral vector (AdV) encoding the luciferase reporter gene (AdV-luc) in a subcutaneous mouse mammary tumor model. Preimmunization resulted in significantly decreased gene expression in tumor and normal tissues (P < 0.01). The decrease was significantly greater in liver than in tumor. Increased AdV doses could be used to overcome the intratumoral inhibition without a concomitant increase in liver transduction. However, preimmunized animals showed greater toxicity than nai;ve animals (P < 0.001). The preimmunized group developed histologic evidence of grade 2-3 hepatic toxicity and increases in the average values of hepatic enzymes. In addition, there was a significant increase in mortality (P < 0.01) in the preimmunized group (12 of 20 animals) compared with the naive group (3 of 20 animals). These findings suggest that although preimmunity can inhibit systemic expression from adenoviral vectors, at high vector doses it may potentiate hepatotoxicity. |
| التعليقات: | Erratum in: Mol Ther. 2002 Oct;6(4):563.. The Bin S [corrected to Teh Bin S]. |
| معلومات مُعتمدة: | CA58204 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Viral Vaccines) |
| تواريخ الأحداث: | Date Created: 20020917 Date Completed: 20030304 Latest Revision: 20190607 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1006/mthe.2002.0669 |
| PMID: | 12231170 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1525-0016 |
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| DOI: | 10.1006/mthe.2002.0669 |