Original Article
Prostate Cancer and Prostatic Diseases advance online publication 23 December 2008; doi: 10.1038/pcan.2008.57
Therapeutic effects of gelatin matrix-embedded IL-12 gene-modified macrophages in a mouse model of residual prostate cancer
K Tabata1, M Watanabe1, K Naruishi1, K Edamura1, T Satoh1, G Yang1, E Abdel Fattah1, J Wang1, A Goltsov1, D Floryk1, S D Soni1, D Kadmon1,2 and T C Thompson1,2,3,4
- 1Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA
- 2Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
- 3Department of Radiology, Baylor College of Medicine, Houston, TX, USA
- 4Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
Correspondence: Dr TC Thompson, Department of Genitourinary Medical Oncology, Unit 1374, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail: timthomp@mdanderson.org
Received 18 August 2008; Revised 13 November 2008; Accepted 13 November 2008; Published online 23 December 2008.
Abstract
We evaluated the potential use of intraoperative gelatin matrix hemostatic sealant (GMHS; FloSeal; Baxter Healthcare) embedded with macrophages (M
) transduced with murine interleukin (IL)-12 recombinant adenoviral vector (G/M
/AdmIL-12) for prevention of recurrence of prostate cancer following radical prostatectomy. Application of G/M
/AdmIL-12 resulted in significant suppression of tumor growth and spontaneous lung metastases, a statistically significant survival advantage of the G/M
/AdmIL-12-treated animals, more efficient trafficking of M
to lymph nodes draining from the prostate and generation of systemic natural killer cell activity and tumor-specific cytolytic T lymphocyte responses compared to the controls in a preclinical mouse model of residual prostate cancer. Our data recommend this treatment as a novel adjuvant for prevention of local recurrence of prostate cancer following radical prostatectomy.
Keywords:
adenoviral vectors, IL-12, matrix-embedded gene-modified cell therapy, residual prostate cancer model
