Suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cell gene delivery vehicles in recurrent glioblastoma multiforme: a first-in-human, dose-escalation, phase I clinical trial.

Autor: Oraee-Yazdani S; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, PO box: 1988873554, Tehran, Iran. Saeed_o_yazdani@sbmu.ac.ir., Tavanaei R; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, PO box: 1988873554, Tehran, Iran., Rostami F; Stem Cell Technology Research Center (STRC), Iran university of medical science (IUMS), Tehran, Iran., Hajarizadeh A; Stem Cell Technology Research Center (STRC), Iran university of medical science (IUMS), Tehran, Iran., Mehrabadi M; Stem Cell Technology Research Center (STRC), Iran university of medical science (IUMS), Tehran, Iran.; Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran., Akhlaghpasand M; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, PO box: 1988873554, Tehran, Iran., Tamaddon M; Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Khannejad S; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, PO box: 1988873554, Tehran, Iran., Yazdani KO; Department of cardiovascular diseases, Zahedan university of medical science, Zahedan, Iran., Zali A; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, PO box: 1988873554, Tehran, Iran.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2023 May 27; Vol. 21 (1), pp. 350. Date of Electronic Publication: 2023 May 27.
DOI: 10.1186/s12967-023-04213-4
Abstrakt: Background: Glioblastoma multiforme (GBM) is associated with remarkably poor prognosis, and its treatment is challenging. This investigation aimed to evaluate the safety of suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying herpes simplex virus-thymidine kinase (HSV-TK) gene for the first time in patients with recurrent GBM.
Methods: This study was a first-in-human, open-label, single-arm, phase I clinical trial with a classic 3 + 3 dose escalation design. Patients who did not undergo surgery for their recurrence were included and received this gene therapy protocol. Patients received the intratumoral stereotactic injection of ADSCs according to the assigned dose followed by prodrug administration for 14 days. The first dosing cohort (n = 3) received 2.5 × 10 5 ADSCs; the second dosing cohort (n = 3) received 5 × 10 5 ADSCs; the third dosing cohort (n = 6) received 10 × 10 5 ADSCs. The primary outcome measure was the safety profile of the intervention.
Results: A total of 12 patients with recurrent GBM were recruited. The median follow-up was 16 (IQR, 14-18.5) months. This gene therapy protocol was safe and well tolerated. During the study period, eleven (91.7%) patients showed tumor progression, and nine (75.0%) died. The median overall survival (OS) was 16.0 months (95% CI 14.3-17.7) and the median progression-free survival (PFS) was 11.0 months (95% CI 8.3-13.7). A total of 8 and 4 patients showed partial response and stable disease, respectively. Moreover, significant changes were observed in volumetric analysis, peripheral blood cell counts, and cytokine profile.
Conclusions: The present clinical trial, for the first time, showed that suicide gene therapy using allogeneic ADSCs carrying the HSV-TK gene is safe in patients with recurrent GBM. Future phase II/III clinical trials with multiple arms are warranted to validate our findings and further investigate the efficacy of this protocol compared with standard therapy alone.
Trial Registration: Iranian Registry of Clinical Trials (IRCT), IRCT20200502047277N2. Registered 8 October 2020, https://www.irct.ir/ .
(© 2023. The Author(s).)
Databáze: MEDLINE
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