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

Authors

Shyam Nyati, Henry Ford HealthFollow
Hans Stricker, Henry Ford HealthFollow
Kenneth N. Barton, Henry Ford HealthFollow
Pin Li, Henry Ford HealthFollow
Mohamed A. Elshaikh, Henry Ford HealthFollow
Haythem Y. Ali, Henry Ford HealthFollow
Stephen L. Brown, Henry Ford HealthFollow
Clara Hwang, Henry Ford HealthFollow
James O. Peabody, Henry Ford HealthFollow
Svend O. Freytag, Henry Ford HealthFollow
Benjamin Movsas, Henry Ford HealthFollow
Farzan Siddiqui, Henry Ford HealthFollow

Recommended Citation

Nyati S, Stricker H, Barton KN, Li P, Elshaikh M, Ali H, Brown SL, Hwang C, Peabody J, Freytag SO, Movsas B, and Siddiqui F. A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate adenocarcinoma. PLoS One 2023; 18(9):e0291315.

Document Type

Article

Publication Date

9-15-2023

Publication Title

PLoS One

Abstract

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.

Medical Subject Headings

Humans; Male; Adenocarcinoma; Adenoviridae; Genetic Therapy; Interleukin-12; Leukocytes, Mononuclear; Prostate; Prostatic Neoplasms; Genes, Transgenic, Suicide; Oncolytic Virotherapy

PubMed ID

37713401

Volume

18

Issue

9

First Page

0291315

Last Page

0291315