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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Direct and distant antitumor effects of a telomerase-selective oncolytic adenoviral agent, OBP-301, in a mouse
1Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Abstract:
We previously constructed OBP-301 (Telomelysin, a telomerase-specific replication-competent adenovirus with human telomerase reverse transcriptase (hTERT) promoter), which showed a strong anticancer effect by inducing cell lysis of human non-small cell lung cancer and colorectal cancer cells. To investigate the utility of OBP-301 for prostate cancer treatment, we herein evaluate the cell killing and antitumor effects. First, in vitro hTERT-specific adenovirus transduction in human prostate cancer cells (LNCaP, PC3, DU145) was confirmed using OBP-401 (Telomelysin-green fluorescent protein (GFP)). There was no detectable GFP transduction in the human prostate normal cells (PrEC, PrSC). Consistently, the cell-killing effect of OBP-301 was observed only in the cancer cells. Second, using an in vivo subcutaneous LNCaP tumor model in nude mice, we demonstrated that three intratumoral OBP-301 injections (10(7) PFU per tumor x 3 days) were sufficient to eradicate the detectable LNCaP prostate tumor. We also demonstrated that the ispilateral treatment with OBP-301 significantly suppressed contralateral LNCaP tumor growth in both sides of the tumor model. Histological and immunohistochemical analyses revealed diffuse oncolytic degeneration and adenoviral E1A protein expression in both sides of the tumors. Therefore, in situ OBP-301 administration could be a promising therapeutic strategy against prostate cancer and its metastatic lesions.
Insights
Telomelysin (OBP-301) effectively targets and destroys prostate cancer cells by leveraging the human telomerase reverse transcriptase (hTERT) promoter. This oncolytic virus demonstrated significant tumor eradication and suppressed metastasis in preclinical models.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Gene therapy
Background:
- OBP-301 (Telomelysin) is a telomerase-specific oncolytic adenovirus with demonstrated efficacy in lung and colorectal cancers.
- Prostate cancer remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of OBP-301 in treating prostate cancer.
- To assess the oncolytic and antitumor effects of OBP-301 in preclinical prostate cancer models.
Main Methods:
- In vitro transduction assays using OBP-401 (Telomelysin-GFP) in human prostate cancer and normal cells.
- In vivo studies using a subcutaneous LNCaP prostate cancer xenograft model in nude mice.
- Histological and immunohistochemical analyses to assess tumor response and viral activity.
Main Results:
- OBP-401 demonstrated hTERT-specific transduction in prostate cancer cells but not in normal prostate cells.
- OBP-301 treatment resulted in complete eradication of LNCaP tumors in vivo.
- OBP-301 treatment suppressed contralateral tumor growth, indicating a potential systemic or abscopal effect.
- Oncolytic degeneration and viral E1A protein expression were observed in treated tumors.
Conclusions:
- OBP-301 exhibits potent oncolytic activity against prostate cancer cells.
- In situ administration of OBP-301 is a promising therapeutic strategy for prostate cancer, including metastatic lesions.
