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.
PloS one. 2023 Sep 15*** epublish ***
Shyam Nyati, Hans Stricker, Kenneth N Barton, Pin Li, Mohamed Elshaikh, Haythem Ali, Stephen L Brown, Clara Hwang, James Peabody, Svend O Freytag, Benjamin Movsas, Farzan Siddiqui
Department of Radiation Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Vattikuti Urology Institute, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Department of Public Health Sciences, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America., Department of Internal Medicine, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan, United States of America.