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Start Over Descriptor "ONCOLYTIC ADENOVIRUSES" Journal oncotarget
3 results on '"ONCOLYTIC ADENOVIRUSES"'

1. A novel oncolytic adenovirus based on simian adenovirus serotype 24

Author

Chao Zhang, Dongming Zhou, Jieyun Yin, Tao Cheng, Yan Zhang, Yufeng Song, and Yudan Chi

Subjects
0301 basic medicine, viruses, Survivin, Gene Expression, Apoptosis, Virus Replication, Inhibitor of Apoptosis Proteins, Mice, 0302 clinical medicine, Cytopathogenic Effect, Viral, Promoter Regions, Genetic, oncolytic adenoviruses, Oncolytic Virotherapy, Mitochondria, Tumor Burden, Oncolytic Viruses, Oncology, Organ Specificity, 030220 oncology & carcinogenesis, Systemic administration, Adenovirus E1A Proteins, Genetic Engineering, Signal Transduction, Research Paper, Oncolytic adenovirus, Genetic Vectors, Biology, Serogroup, p53-independent mitochondrial apoptosis, 03 medical and health sciences, AdC7, Immunity, Cell Line, Tumor, tumor treatment, Animals, Humans, Genetic Therapy, Virology, Xenograft Model Antitumor Assays, Oncolytic virus, Disease Models, Animal, 030104 developmental biology, Viral replication, Molecular virology, Adenoviruses, Simian, Tumor Suppressor Protein p53, chimpanzee adenoviruses, Gene Deletion
Abstract

// Tao Cheng 1 , Yufeng Song 1 , Yan Zhang 1 , Chao Zhang 1 , Jieyun Yin 1 , Yudan Chi 1 , Dongming Zhou 1 1 Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai 200031, China Correspondence to: Dongming Zhou, email: dmzhou@sibs.ac.cn Keywords: oncolytic adenoviruses, AdC7, chimpanzee adenoviruses, p53-independent mitochondrial apoptosis, tumor treatment Received: October 12, 2016 Accepted: February 20, 2017 Published: March 02, 2017 ABSTRACT Among the oncolytic virotherapy, an emerging treatment for tumor, adenoviruses are widely used at present in preclinical and clinical trials. Traditionally, oncolytic adenoviruses were developed based on the human adenovirus serotype 5 (AdHu5). However, AdHu5 has the drawbacks of preexisting anti-AdHu5 immunity in most populations, and extensive sequestration of Adhu5 by the liver through hexon, blood coagulation factor X (FX), and FX receptor interactions. To tackle these problems, we explored a novel oncolytic adenovirus AdC7-SP/E1A-ΔE3 for cancer treatment. AdC7-SP/E1A-ΔE3 was constructed by replacing the E1A promoter with tumor specific promoter survivin promoter and deleting E3 region using direct cloning methods based on simian adenovirus serotype 24 (namely AdC7). We showed that AdC7-SP/E1A-ΔE3 significantly killed tumor cell lines NCI-H508 and Huh7, and inhibited tumor growth in both NCI-H508 and Huh7 xenograft tumor models. Importantly, AdC7-SP/E1A-ΔE3 exhibited the antitumor efficacy via systemic administration. Mechanistically, infected cells were killed by AdC7-SP/E1A-ΔE3 via the p53-independent mitochondrial apoptosis pathway in which phosphorylation of BAD markedly declined and the expresses of Bik significantly went up. Therefore, AdC7-SP/E1A-ΔE3 is a promising candidate for liver and colon tumor treatment.

Published
2016

2. Mesenchymal stem cell carriers enhance antitumor efficacy of oncolytic adenoviruses in an immunocompetent mouse model.

Author

Rincón E, Cejalvo T, Kanojia D, Alfranca A, Rodríguez-Milla MÁ, Gil Hoyos RA, Han Y, Zhang L, Alemany R, Lesniak MS, and García-Castro J

Subjects
Animals, Cell Line, Tumor, Cell Movement, Cell Survival genetics, Cytokines metabolism, Disease Models, Animal, Gene Expression, Genes, Reporter, Genetic Therapy, Humans, Immunotherapy, Inflammation Mediators metabolism, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Mice, Transduction, Genetic, Xenograft Model Antitumor Assays, Adenoviridae genetics, Genetic Vectors genetics, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells metabolism, Oncolytic Virotherapy, Oncolytic Viruses genetics
Abstract

Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown. In this study, we used the syngeneic murine CMT64 cell line as a human adenovirus-semi-permissive tumor model and demonstrate the homing capacity of mouse Celyvir (mCelyvir) to CMT64 tumors. We found that the combined treatment of mCelyvir and intratumoral injections (i.t.) of ICOVIR5 was more effective than treatment with i.t. ICOVIR5 alone. Interestingly, the superior therapeutic effect of the combined therapy was associated with a higher tumor infiltration of CD8+ and CD4+ T cells. Our findings suggest that the use of MSCs as carriers of oncolytic adenovirus can improve the clinical efficacy of anti-cancer virotherapy, not only by driving the adenovirus to tumors, but also through their potential to recruit T cells.

Published
2017
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3. A novel oncolytic adenovirus based on simian adenovirus serotype 24.

Author

Cheng T, Song Y, Zhang Y, Zhang C, Yin J, Chi Y, and Zhou D

Subjects
Adenovirus E1A Proteins genetics, Animals, Apoptosis genetics, Cell Line, Tumor, Cytopathogenic Effect, Viral, Disease Models, Animal, Gene Deletion, Gene Expression, Genetic Engineering, Genetic Therapy, Genetic Vectors administration & dosage, Genetic Vectors adverse effects, Humans, Inhibitor of Apoptosis Proteins genetics, Mice, Mitochondria genetics, Oncolytic Virotherapy, Organ Specificity genetics, Promoter Regions, Genetic, Serogroup, Signal Transduction, Survivin, Tumor Burden, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Virus Replication, Xenograft Model Antitumor Assays, Adenoviruses, Simian classification, Adenoviruses, Simian genetics, Genetic Vectors genetics, Oncolytic Viruses genetics
Abstract

Among the oncolytic virotherapy, an emerging treatment for tumor, adenoviruses are widely used at present in preclinical and clinical trials. Traditionally, oncolytic adenoviruses were developed based on the human adenovirus serotype 5 (AdHu5). However, AdHu5 has the drawbacks of preexisting anti-AdHu5 immunity in most populations, and extensive sequestration of Adhu5 by the liver through hexon, blood coagulation factor X (FX), and FX receptor interactions. To tackle these problems, we explored a novel oncolytic adenovirus AdC7-SP/E1A-ΔE3 for cancer treatment. AdC7-SP/E1A-ΔE3 was constructed by replacing the E1A promoter with tumor specific promoter survivin promoter and deleting E3 region using direct cloning methods based on simian adenovirus serotype 24 (namely AdC7). We showed that AdC7-SP/E1A-ΔE3 significantly killed tumor cell lines NCI-H508 and Huh7, and inhibited tumor growth in both NCI-H508 and Huh7 xenograft tumor models. Importantly, AdC7-SP/E1A-ΔE3 exhibited the antitumor efficacy via systemic administration. Mechanistically, infected cells were killed by AdC7-SP/E1A-ΔE3 via the p53-independent mitochondrial apoptosis pathway in which phosphorylation of BAD markedly declined and the expresses of Bik significantly went up. Therefore, AdC7-SP/E1A-ΔE3 is a promising candidate for liver and colon tumor treatment.

Published
2017
Full Text
View/download PDF

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