Enhanced antitumor efficacy of telomerase‐selective oncolytic adenoviral agent OBP‐401 with docetaxel: Preclinical evaluation of chemovirotherapy
Abstract
Oncolytic adenoviruses are being developed as novel anticancer therapeutics and currently undergoing clinical trials. We previously demonstrated that telomerase‐specific replication‐competent adenovirus (Telomelysin: OBP‐301), in which the human telomerase reverse transcriptase (hTERT) promoter regulates viral replication, efficiently killed human tumor cells. We further constructed OBP‐401 (Telomelysin‐GFP) that expresses the green fluorescent protein (GFP) reporter gene under the control of the cytomegalovirus promoter in the E3 region to monitor viral distribution. Here, we examined the feasibility of a single‐agent therapy with OBP‐401 as well as of combining OBP‐401 with chemotherapeutic agents. Infection of OBP‐401 alone or followed by the treatment of a chemotherapeutic drug, docetaxel (Taxotere), resulted in a profound in vitro cytotoxicity and GFP expression in various human cancer cell lines originating from different organs (lung, colon, esophagus, stomach, liver and prostate), although the magnitude of antitumor effect varied among the cell types. Other chemotherapeutic drugs such as vinorelbine (Navelbine) and SN38 (the potent active metabolite of irinotecan) combined with OBP‐401 also inhibited the growth of human cancer cells. Quantitative real‐time PCR analysis demonstrated that docetaxel did not affect viral replication. For in vivo evaluation, nu/nu mice xenografted with H1299 human lung tumor received intratumoral injection of OBP‐401 and intraperitoneal administration of docetaxel. Analysis of growth of implanted tumors showed a significant, therapeutic synergism, although OBP‐401 alone and docetaxel alone showed modest inhibition of tumor growth. Thus, OBP‐401 in combination with docetaxel efficiently enhances the antitumor efficacy both in vitro and in vivo, and the outcome has important implications for tumor‐specific oncolytic chemovirotherapies for human cancers. © 2006 Wiley‐Liss, Inc.
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Intratumoral Telomelysin combined with intraperitoneal docetaxel produces synergistic effects in xenografts.
“Of particular interest were the synergistic effects of Telomelysin when it was administrated intratumorally to xenografts in combination with intraperitoneal administration of docetaxel.”
From Understanding and exploiting <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [111]
Combining Telomelysin with docetaxel, vinorelbine, or SN38 enhances Telomelysin cytotoxicity in vitro in multiple organs, including lung, colon, esophagus, stomach, liver, and prostate.
“Combination with docetaxel, vinorelbine (Nevelbine), or SN38 (active metabolite of irinotecan) has been confirmed in vitro to enhance Telomelysin cytotoxicity in different organs including the lung, colon, esophagus, stomach, liver, and prostate.(111)”
From Understanding and exploiting <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [111]
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Self-citation
- Authors
- Fujiwara, T., Kagawa, S., Kishimoto, H., Endo, Y., Hioki, M., Ikeda, Y., Sakai, R., Urata, Y., Tanaka, N., & Fujiwara, T.
- Affiliations
- Okayama University (JP)
- Oncolys BioPharma (Japan) (JP)
- Corresponding author
- Fujiwara, Toshiyoshi
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2006-04-27
- Volume
- 119
- Issue
- 2
- Pages
- 432-440
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2023966374
- Cited by
- 73
- References
- 31
- Citations by year
- 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 6 · 2013: 6 · 2012: 4
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- oncolytic adenovirus, telomerase, human telomerase reverse transcriptase promoter, docetaxel, combination therapy, antitumor efficacy, vinorelbine, SN-38, irinotecan, tumor xenografts, viral replication, GFP reporter
- MeSH terms
- Docetaxel, Vinorelbine, Adenoviridae, Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Antineoplastic Agents, Phytogenic, Carcinoma, Carcinoma, Non-Small-Cell Lung, Drug Carriers, Esophageal Neoplasms, Feasibility Studies, Humans, Lung Neoplasms, Mice, Nude, Neoplasms, Stomach Neoplasms, Transplantation, Heterologous, Vinblastine, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Polymerase Chain Reaction, Telomerase, Taxoids, Cell Line, Tumor, Green Fluorescent Proteins, Mice
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