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A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2003 Oct; Vol. 10 (10), pp. 755-63. - Publication Year :
- 2003
-
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.
- Subjects :
- Adjuvants, Immunologic
Aged
Cells, Cultured
Dendritic Cells immunology
Disease Susceptibility
Genetic Therapy adverse effects
Humans
Immunotherapy adverse effects
Inflammation immunology
Inflammation pathology
Interferon-gamma immunology
Interferon-gamma metabolism
Interleukin-2 adverse effects
Interleukin-4 immunology
Male
Middle Aged
Prostate-Specific Antigen analysis
Prostatic Neoplasms genetics
T-Lymphocytes immunology
Treatment Outcome
Vaccination
Adenoviridae genetics
Genetic Therapy methods
Immunotherapy methods
Interleukin-2 genetics
Interleukin-2 therapeutic use
Prostatic Neoplasms immunology
Prostatic Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0929-1903
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 14502228
- Full Text :
- https://doi.org/10.1038/sj.cgt.7700626