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

doi:10.1038/sj.cgt.7700626

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

Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

49 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 language	English (US)
Pages (from-to)	755-763
Number of pages	9
Journal	Cancer Gene Therapy
Volume	10
Issue number	10
DOIs	https://doi.org/10.1038/sj.cgt.7700626
State	Published - Oct 2003

Keywords

Adenovirus
Adjuvant therapy
IL-2
Prostate cancer

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cancer Research

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10.1038/sj.cgt.7700626

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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

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

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.",

keywords = "Adenovirus, Adjuvant therapy, IL-2, Prostate cancer",

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

note = "Funding Information: 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.",

year = "2003",

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doi = "10.1038/sj.cgt.7700626",

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AU - Trudel, Suzane

AU - Trachtenberg, John

AU - Toi, Ants

AU - Sweet, Joan

AU - Li, Zhi Hua

AU - Jewett, Michael

AU - Tshilias, John

AU - Zhuang, Li Hue

AU - Hitt, Mary

AU - Wan, Yonghong

AU - Gauldie, Jack

AU - Graham, Frank L.

AU - Dancey, Janet

AU - Stewart, A. Keith

N1 - Funding Information: 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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N2 - 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.

AB - 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.

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KW - IL-2

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

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Keywords

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