Related Experiment Video
Updated: May 29, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Treatment of mesothelioma with gene-modified PA1STK cells and ganciclovir: a phase I study
P Schwarzenberger1, P Byrne, R Gaumer
1Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA. poschwarz@yahoo.com
Abstract:
Mesothelioma is an incurable cancer of the pleura with a life expectancy of less than 1 year. On the basis of in vivo efficacy seen with the herpes simplex virus type 1 thymidine kinase (HSVtk) suicide gene-modified PA1STK cell line and ganciclovir (GCV) in a murine model of mesothelioma, a first in humans, clinical trial was designed for this therapeutic concept. The study was a phase I clinical trial using direct infusion of escalating doses of HSVtk suicide gene-modified PA1STK cells directly into tumor-associated pleural effusions followed by 7 days of intravenous GCV infusion. Therapeutic levels of GCV in both serum and pleura were achieved within 1 h, and GCV trough levels remained above the therapeutic threshold for the duration of GCV treatment. The treatment was well tolerated without any Grade 3 or 4 toxicity observed. Significant inductions of both Th1 and Th2 cytokines up to 20-fold over baseline were observed. No significant differences were seen between serum and pleura cytokine profiles, with the exception of interleukin-10, which was consistently elevated in the pleura specimens. No objective radiographic responses were observed. The data indicate significant immunological responses and validate the principal anti-tumor mechanisms observed in preclinical models of mesothelioma in a human clinical trial.
Insights
This phase I clinical trial explored a novel mesothelioma treatment using herpes simplex virus type 1 thymidine kinase (HSVtk) gene-modified cells and ganciclovir (GCV). The therapy demonstrated significant immunological responses and was well-tolerated in patients with pleural mesothelioma.
Area of Science:
- Oncology
- Gene Therapy
- Immunology
Background:
- Mesothelioma is an incurable pleural cancer with a poor prognosis.
- Preclinical studies showed efficacy of herpes simplex virus type 1 thymidine kinase (HSVtk) suicide gene therapy in mesothelioma models.
Purpose of the Study:
- To evaluate the safety and immunological effects of HSVtk suicide gene-modified PA1STK cells followed by ganciclovir (GCV) in a phase I clinical trial for mesothelioma.
- To assess therapeutic drug levels and cytokine profiles in patients with malignant pleural effusion.
Main Methods:
- Phase I clinical trial involving direct infusion of escalating doses of HSVtk gene-modified PA1STK cells into pleural effusions.
- Followed by a 7-day intravenous infusion of ganciclovir (GCV).
- Monitoring of drug levels in serum and pleural fluid, and assessment of cytokine induction (Th1, Th2, IL-10).
Main Results:
- Therapeutic levels of GCV were achieved in serum and pleural fluid.
- The treatment was well-tolerated with no Grade 3 or 4 toxicity.
- Significant induction of Th1 and Th2 cytokines (up to 20-fold) was observed, with elevated interleukin-10 in pleural fluid.
Conclusions:
- The HSVtk suicide gene therapy with GCV is safe and induces significant immunological responses in mesothelioma patients.
- The study validates preclinical anti-tumor mechanisms in a human clinical setting.
- Further investigation is warranted for this promising mesothelioma treatment strategy.
