Intraprostatic distribution and long-term follow-up after AdV-tk immunotherapy as neoadjuvant to surgery in patients with prostate cancer

A. Rojas-Martínez, A. G. Manzanera, S. W. Sukin, J. Esteban-María, J. F. González-Guerrero, L. Gomez-Guerra, R. Garza-Guajardo, J. P. Flores-Gutiérrez, G. Elizondo Riojas, I. Delgado-Enciso, R. Ortiz-López, L. K. Aguilar, E. B. Butler, H. A. Barrera-Saldaña, E. Aguilar-Cordova

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

A phase I-II study to evaluate gene-mediated cytotoxic immunotherapy in newly diagnosed prostate cancer before radical prostatectomy was conducted in Monterrey, Mexico. First, to investigate delivery of adenovirus to the prostate, fluorescently labeled vector was injected into fresh prostatectomy specimens and distribution was visually analyzed. The optimal volume and site instillation was then used for transrectal ultrasound guided intraprostatic injection in 10 patients with adenocarcinoma scheduled for radical prostatectomy. Each received two apical and two basal 0.5 ml injections of AdV-tk for a total of 1 × 1011 vp followed by 14 days of prodrug. Nine patients continued to tumor resection: six high risk, one intermediate and two low risk. In vivo vector distribution was analyzed from the resected tissue of four patients. Patients were monitored for tumor progression and acute and long-term safety. For vector delivery, two apical and two basal injections of 0.5 ml led to optimal organ-wide distribution ex vivo and in vivo. Cytotoxicity was evidenced by transient rise in PSA and tumor histology. There were no significant adverse events deemed related to the treatment and no late toxicities after median follow-up of 11.3 years. All six high-risk patients had positive surgical margins and one had seminal vesicle involvement. Despite slow PSA rise post surgery in three of these patients, none developed metastases. The intermediate- and low-risk patients had complete resections and none have progressed. In conclusion, in vivo transrectal ultrasound guided instillation of an adenoviral vector into four sites in the prostate was practical as an outpatient procedure, well tolerated and led to distribution throughout the intraprostatic tumor mass. AdV-tk demonstrated no significant acute or late toxicities. Trends in PSA and disease progression conveyed the possibility of a sustained immune response against residual disease.

Original languageEnglish (US)
Pages (from-to)642-649
Number of pages8
JournalCancer Gene Therapy
Volume20
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • androgen deprivation therapy
  • gene-mediated cytotoxic immunotherapy
  • intra-tumor vector distribution
  • long-term safety
  • prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

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