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Published on: October 10, 2025
Development of human chorionic gonadotropin subunit-beta promoter-based toxic gene therapy for testicular cancer
Toshiro Shirakawa1, Akinobu Gotoh, Zhujun Zhang
1International Center for Medical Research, Kobe University School of Medicine, Kobe, Japan.
Objectives:
To develop a new toxic gene therapy using the tissue-specific human chorionic gonadotropin-beta (hCG-beta) promoter for testicular cancer. Although most patients presenting with disseminated testicular tumor are cured through the use of chemotherapy with or without surgery, those patients with relapse after initial therapy present a difficult clinical problem. The serum tumor marker hCG-beta is frequently elevated in patients with testicular cancer, and the pretreatment and post-treatment levels of serum hCG-beta are highly predictive of treatment outcome.
Methods:
Human testicular embryonal carcinoma cell line, NEC 8, a human prostate cancer cell line, PC-3, and a human bladder cancer cell line, WH, were used in this study. A transient expression experiment was used to analyze the activity of a 729-bp hCG-beta promoter in all three cell lines. A recombinant adenovirus carrying thymidine kinase (Ad-hCG-beta-TK) under control of the hCG-beta promoter was generated. The tissue-specific activity of Ad-hCG-beta-TK was tested in vitro and in vivo.
Results:
The hCG-beta promoter had significantly greater activity in the hCG-beta-producing cell line (NEC 8) than in the non-hCG-beta-producing cell lines (PC-3 and WH). In vitro, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 growth but not PC-3 or WH cell growth. In vivo, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 subcutaneous tumor growth in nude mice.
Conclusions:
In this study, we explored the possibility of developing a new therapeutic agent to target and induce the killing of testicular germ cell tumor selectively by using tissue-specific hCG-beta promoters.
Insights
This study developed a novel gene therapy for testicular cancer using the human chorionic gonadotropin-beta (hCG-beta) promoter. The hCG-beta promoter selectively targeted and inhibited tumor growth in preclinical models, offering a promising new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Testicular cancer relapse after chemotherapy presents a clinical challenge.
- Serum human chorionic gonadotropin-beta (hCG-beta) is a key tumor marker in testicular cancer.
- hCG-beta levels predict treatment outcomes, indicating its potential as a therapeutic target.
Purpose of the Study:
- To develop a targeted gene therapy for testicular cancer using the hCG-beta promoter.
- To investigate the tissue-specific activity of the hCG-beta promoter for selective cancer cell killing.
- To assess the efficacy of a novel gene therapy agent in preclinical models.
Main Methods:
- Utilized human testicular (NEC 8), prostate (PC-3), and bladder (WH) cancer cell lines.
- Analyzed hCG-beta promoter activity using transient expression experiments.
- Generated a recombinant adenovirus (Ad-hCG-beta-TK) and tested its tissue-specific activity in vitro and in vivo.
Main Results:
- The hCG-beta promoter showed significantly higher activity in hCG-beta-producing NEC 8 cells compared to PC-3 and WH cells.
- In vitro, Ad-hCG-beta-TK with acyclovir selectively inhibited NEC 8 cell growth.
- In vivo, Ad-hCG-beta-TK with acyclovir significantly suppressed subcutaneous NEC 8 tumor growth in nude mice.
Conclusions:
- The study demonstrates the potential of tissue-specific hCG-beta promoters for targeted testicular germ cell tumor therapy.
- This approach offers a strategy to selectively kill cancer cells, minimizing damage to healthy tissues.
- Further development of this gene therapy could provide a new treatment option for relapsed testicular cancer.
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