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

Cancer Gene Therapy volume 10, pages 755–763 (2003)Cite this article

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 γ-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.

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Acknowledgements

This work was supported by funding from the Canadian Institutes for Health Research, CANVAC network of centers of excellence, The Princess Margaret Hospital Foundation, The Moog Family, The ABC group and The Nelson Arthur Hyland Foundation. Dr Trudel is supported by a research fellowship of the National Cancer Institute of Canada. We would like to thank Greg Pond for his assistance with the statistical analysis.

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Authors and Affiliations

  1. Division of Hematology-Oncology and Urology, The Princess Margaret Hospital, 610 University Avenue, Toronto, M5G 2M9, Ontario, Canada

    Suzane Trudel, John Trachtenberg, Ants Toi, Joan Sweet, Zhi Hua Li, Michael Jewett, John Tshilias, Li Hue Zhuang & A Keith Stewart

  2. Department of Biology and Pathology, McMaster University, Hamilton, Ontario, Canada

    Mary Hitt, Yonghong Wan, Jack Gauldie & Frank L Graham

  3. National Cancer Institute, Rockville, Maryland, USA

    Janet Dancey

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  1. Suzane Trudel
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Correspondence to A Keith Stewart.

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Trudel, S., Trachtenberg, J., Toi, A. et al. A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer. Cancer Gene Ther 10, 755–763 (2003). https://doi.org/10.1038/sj.cgt.7700626

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