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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.

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.

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

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

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