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Prostate Cancer Most common malignancy and 2nd most common cause of cancer death in men in US 179,300 cases in 1999 37,000 deaths External beam radiation therapy (EBRT) is a common and standard treatment Relapse rates after EBRT range from ~10-30% of “low risk patient” to 30-40% of patients with increased risk factors After relapse, cause specific survival at 5 yrs. is 75%

Prostate Cancer Salvage Therapies Brachytherapy Surgery Cryotherapy Hormonal therapy EBRT All have increased toxicities and reduced effectiveness as compared to primary therapy

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Thyroid Cancer Therapy Radioiodine therapy 131I of differentiated thyroid cancer represents the most effective form of systemic radiotherapy available to the clinician today Thyroid cancer can be effectively treated by radioiodine therapy because of the ability of thyroidal cells to concentrate iodine from plasma This iodide trapping activity of the thyroid gland is due to expression of the sodium iodide symporter -- NIS

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NIS as a Therapeutic Gene

NIS Expression & Clinical Use NIS is primarily expressed in thyroid gland NIS expression has also been detected in extrathyroidal tissues including salivary glands, lacrimal gland, gastric and colonic mucosa, mammary gland, and in renal tubular cells Clinical tests including radioiodine uptake test, perchlorate discharge test and thyroid scintigraphy are based upon a functionally intact NIS NIS expression in thyroid cancer allows imaging as well as therapy by radioiodine administration

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Phase I Trial of NIS Mediated Gene Therapy for Prostate Ca

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Phase I Trial of NIS Mediated Gene Therapy for Prostate Ca

Phase I Trial of NIS Mediated Gene Therapy for Prostate Ca

Toxicity/Biodistribution Studies

Toxicity/Biodistribution Studies

Toxicity/Biodistribution Studies

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Toxicity/Biodistribution Studies

Toxicity/Biodistribution Studies

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Toxicity/Biodistribution Studies Summary of Results No animal died or demonstrated toxic behaviors Biodistribution results (PCR) being completed now No thyroid histologic changes Mild TSH changes

Toxicity/Biodistribution Studies No tissue/organ changes except: Focal acute and chronic prostatitis with highest dose virus Positive NIS immunostaining in liver with max IV dose with normal histology Recent splenic infarct in one animal receiving max IV dose Focal inflammation in lung of one animal that received max prostate dose and radioiodine and two that received vehicle only

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NIS as a Therapeutic Gene