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Updated: Jul 16, 2026
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
Published on: April 27, 2018
Phase I trial of replication-competent adenovirus-mediated suicide gene therapy combined with IMRT for prostate
Svend O Freytag1, Benjamin Movsas, Ibrahim Aref
1Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA. sfreyta1@hfhs.org
Abstract:
Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment in which an oncolytic adenovirus armed with chemo-radiosensitizing genes is used to destroy tumor cells. Previously, we evaluated the toxicity and efficacy of this approach in two clinical trials of prostate cancer using a first-generation adenovirus. Here, we report the toxicity and preliminary efficacy of this approach in combination with intensity-modulated radiotherapy (IMRT) in patients with newly diagnosed prostate cancer using an improved, second-generation adenovirus. The investigational therapy was associated with low toxicity, and there were no dose-limiting toxicities or treatment-related serious adverse events. Relative to a previous trial using a first-generation adenovirus, there was no increase in hematologic, hepatic, gastrointestinal (GI), or genitourinary (GU) toxicities. Post-treatment prostate biopsies yielded provocative preliminary results. When the results of two similar trials were combined, 22% of evaluable patients were positive for adenocarcinoma at their last biopsy, which is better than expected (>or=40%) for this cohort of patients (P=0.038). When the results were categorized by prognostic risk, most of the treatment effect was observed in the intermediate-risk group, with 0 of 12 patients (0%) being positive for cancer at their last biopsy (P<0.01). These results further demonstrate the safety of this investigational approach and raise the possibility that it may have the potential to improve the outcome of conformal radiotherapy in select patient groups.
Insights
Second-generation adenovirus suicide gene therapy combined with IMRT shows low toxicity in prostate cancer patients. Preliminary results suggest improved outcomes, particularly for intermediate-risk patients, warranting further investigation.
Area of Science:
- Oncology
- Gene Therapy
- Radiation Oncology
Background:
- Replication-competent adenovirus-mediated suicide gene therapy utilizes oncolytic adenoviruses with chemo-radiosensitizing genes to target tumor cells.
- Previous trials evaluated first-generation adenovirus toxicity and efficacy in prostate cancer.
- An improved, second-generation adenovirus was used in this study.
Purpose of the Study:
- To report the toxicity and preliminary efficacy of second-generation adenovirus suicide gene therapy combined with intensity-modulated radiotherapy (IMRT) in newly diagnosed prostate cancer patients.
- To compare toxicity with previous trials using a first-generation adenovirus.
- To assess treatment outcomes based on prognostic risk.
Main Methods:
- Phase I/II clinical trial involving newly diagnosed prostate cancer patients.
- Administration of second-generation replication-competent adenovirus combined with IMRT.
- Evaluation of toxicity (hematologic, hepatic, GI, GU) and serious adverse events.
- Analysis of post-treatment prostate biopsy results for adenocarcinoma positivity.
- Stratification of results by prognostic risk.
Main Results:
- The investigational therapy demonstrated low toxicity with no dose-limiting toxicities or treatment-related serious adverse events.
- No increase in hematologic, hepatic, gastrointestinal (GI), or genitourinary (GU) toxicities was observed compared to first-generation adenovirus trials.
- Combined results from two trials showed 22% of evaluable patients positive for adenocarcinoma post-treatment, which was statistically better than the expected rate (>40%) for this cohort (P=0.038).
- The intermediate-risk group showed a significant treatment effect, with 0% of patients positive for cancer at last biopsy (P<0.01).
Conclusions:
- Second-generation adenovirus-mediated suicide gene therapy combined with IMRT is safe and well-tolerated in newly diagnosed prostate cancer patients.
- The approach shows potential for improving outcomes in select patient groups, especially intermediate-risk individuals, when combined with conformal radiotherapy.
- Further investigation is warranted to confirm these preliminary efficacy findings.
