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 10(9), 5 x 10(9) and 10(10) 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 gamma-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.
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000276:Adjuvants, Immunologic; D000368:Aged; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000009:adverse effects / Q000235:genetics* / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen