Liposomal Enhancement of the Antitumor Activity of Conditionally Replication-Competent Adenoviral Plasmids

التفاصيل البيبلوغرافية
العنوان: Liposomal Enhancement of the Antitumor Activity of Conditionally Replication-Competent Adenoviral Plasmids
المؤلفون: Patricia, Yotnda, A R, Davis, M J, Hicks, N S, Templeton, M K, Brenner, M K, Benner
المصدر: Molecular Therapy. 9(4):489-495
بيانات النشر: Elsevier BV, 2004.
سنة النشر: 2004
مصطلحات موضوعية: Time Factors, Genetic Vectors, Antineoplastic Agents, Virus Replication, medicine.disease_cause, Virus, Adenoviridae, Cell Line, Viral vector, Mice, Immune system, Plasmid, Cell Line, Tumor, Neoplasms, Drug Discovery, medicine, Genetics, Animals, Humans, Neutralizing antibody, Molecular Biology, Pharmacology, biology, Genetic Therapy, Transfection, Genes, p53, Immunohistochemistry, Virology, Viral replication, Liposomes, biology.protein, Molecular Medicine, Neoplasm Transplantation, Plasmids
الوصف: Many human tumors have a functional deficiency in p53. Numerous studies have taken advantage of this phenomenon to use a conditionally replication-competent adenovirus (Ad dl1520) that will grow in and lyse tumor cells while sparing normal tissues. However, success has been limited, in part due to difficulties in reaching a sufficiently high proportion of tumor cells. Preexisting or developing immune responses directed toward viral proteins further decrease the efficacy of the approach. We have developed a liposome-encapsulated conditionally replication-competent plasmid based on the dl1520 virus. Like the parent virus, this plasmid generates infectious particles following transfection of p53-defective, but not p53-wild-type tumor cells, but unlike the parent virus it is able to infect CAR-negative tumor cells. The antitumor efficacy of this infectious plasmid was demonstrated in mice with xenografted human tumors, in which it was active after both local and intravenous administration for subcutaneous tumors and following intravenous administration for disseminated malignancy. Activity was retained systemically, even in the presence of neutralizing antibody. Such liposomally encapsulated conditionally replication-competent plasmids may complement the use of conventional viral particles, particularly in settings in which liver uptake of adenoviral vector is undesirable or there are problematic inhibitory effects from humoral immune responses.
تدمد: 1525-0016
DOI: 10.1016/j.ymthe.2004.01.018
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f36799223413069517293ac78301a20cTest
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....f36799223413069517293ac78301a20c
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15250016
DOI:10.1016/j.ymthe.2004.01.018