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

  1. 1Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA
  2. 2Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
  3. 3Department of Radiology, Baylor College of Medicine, Houston, TX, USA
  4. 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.

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Abstract

We evaluated the potential use of intraoperative gelatin matrix hemostatic sealant (GMHS; FloSeal; Baxter Healthcare) embedded with macrophages (Mphi) transduced with murine interleukin (IL)-12 recombinant adenoviral vector (G/Mphi/AdmIL-12) for prevention of recurrence of prostate cancer following radical prostatectomy. Application of G/Mphi/AdmIL-12 resulted in significant suppression of tumor growth and spontaneous lung metastases, a statistically significant survival advantage of the G/Mphi/AdmIL-12-treated animals, more efficient trafficking of Mphi 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

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