A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer

Suzane Trudel, John Trachtenberg, Ants Toi, Joan Sweet, Zhi Hua Li, Michael Jewett, John Tshilias, Li Hue Zhuang, Mary Hitt, Yonghong Wan, Jack Gauldie, Frank L. Graham, Janet Dancey, A. Keith Stewart

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Preclinical studies demonstrate that intratumoral delivery of adenovirus expressing IL-2 eradicates pre-established tumors in mice and confers immune protection from rechallenge. To explore the activity of AdCAIL-2 in prostate cancer, a Phase I clinical trial was conducted in patients with localized disease and Gleason score >7 or prostate-specific antigen (PSA) > 10 plus Gleason score 7. A total of 12 patients were injected 4 weeks prior to prostatectomy in a dose-escalation study at doses of 109, 5 × 109 and 1010 PFU of virus. No dose-limiting toxicity was observed. Side effects included perineal discomfort, hematuria, flu-like symptoms in two patients and urinary hesitancy in one patient. Pathology demonstrated an inflammatory response consisting predominantly of CD3+CD8+ T lymphocytes with areas of tumor necrosis. Intracellular cytokine staining of tumor-infiltrating lymphocytes demonstrated increases in both Υ-interferon and IL-4 secreting T cells after vaccination. PSA levels fell in five of five evaluable patients treated at the lowest dose (mean decline of 33.3%, range 17-69%). At higher doses, PSA values initially increased after injection, then fell to baseline prior to surgery. This trial demonstrates the feasibility and safety of intraprostatic adenovector-mediated IL-2 gene delivery.

Original languageEnglish (US)
Pages (from-to)755-763
Number of pages9
JournalCancer Gene Therapy
Volume10
Issue number10
DOIs
StatePublished - Oct 2003

Keywords

  • Adenovirus
  • Adjuvant therapy
  • IL-2
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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    Trudel, S., Trachtenberg, J., Toi, A., Sweet, J., Li, Z. H., Jewett, M., Tshilias, J., Zhuang, L. H., Hitt, M., Wan, Y., Gauldie, J., Graham, F. L., Dancey, J., & Stewart, A. K. (2003). A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer. Cancer Gene Therapy, 10(10), 755-763. https://doi.org/10.1038/sj.cgt.7700626