A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate adenocarcinoma.

Autor: Nyati S; Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America.; Department of Radiology, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, United States of America., Stricker H; Vattikuti Urology Institute, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Barton KN; Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Li P; Department of Public Health Sciences, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Elshaikh M; Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Ali H; Department of Internal Medicine, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Brown SL; Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America.; College of Human Medicine, Michigan State University, East Lansing, Michigan, United States of America., Hwang C; Department of Internal Medicine, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Peabody J; Vattikuti Urology Institute, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Freytag SO; Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Movsas B; Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America.; College of Human Medicine, Michigan State University, East Lansing, Michigan, United States of America., Siddiqui F; Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Sep 15; Vol. 18 (9), pp. e0291315. Date of Electronic Publication: 2023 Sep 15 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0291315
Abstrakt: In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.
Competing Interests: KNB and SOF hold a patent “Methods and Composition for Cancer Therapy Using a Novel Adenovirus” (#7,815,902 B2) for an adenovirus like the one used in this study, BM: Research support from Varian, ViewRay and Philips (no direct conflict), FS: Varian Medical Systems, Inc- Honorarium and travel reimbursement for lectures and talks, Varian Noona- Medical Advisory Board member- receive honorarium, CW: Clara Hwang: Stock holdings in Johnson and Johnson; research funding to institution from Merck, Bausch Health, Genentech, Bayer, and AstraZeneca, consultant fees from Tempus, Genzyme, and EMD Sorono, speaking fees from OncLive/MJH Life Sciences, travel fees from Merck, all outside the submitted work. SN: The work presented was partly supported by NIH-R21-CA252010 (co-PIs: MD Green and S Nyati). SB: The work presented was partly supported by NIH-R01-CA218596 (co-PIs: JR Ewing and S Brown). HA: participate in research activities with Novartis, Merck, Astra-Zeneca, Grail, and Pfizer. Receives consultation Honorarium from Astra-Zeneca, Seagen, Pfizer, OBI, cardinal health and Regeneron. HS, MA, JP, PL: no COI. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2023 Nyati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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