GLIPR1 tumor suppressor gene expressed by adenoviral vector as neoadjuvant intraprostatic injection for localized intermediate or high-risk prostate cancer preceding radical prostatectomy

Clin Cancer Res. 2011 Nov 15;17(22):7174-82. doi: 10.1158/1078-0432.CCR-11-1899. Epub 2011 Sep 20.


Background: GLIPR1 is upregulated by p53 in prostate cancer cells and has preclinical antitumor activity. A phase I clinical trial was conducted to evaluate the safety and activity of the neoadjuvant intraprostatic injection of GLIPR1 expressing adenovirus for intermediate or high-risk localized prostate cancer before radical prostatectomy (RP).

Methods: Eligible men had localized prostate cancer (T1-T2c) with Gleason score greater than or equal to 7 or prostate-specific antigen 10 ng/mL or more and were candidates for RP. Patients received the adenoviral vector expressing the GLIPR1 gene by a single injection into the prostate followed four weeks later by RP. Six viral particle (vp) dose levels were evaluated: 10(10), 5 × 10(10), 10(11), 5 × 10(11), 10(12), and 5 × 10(12) vp.

Results: Nineteen patients with a median age of 64 years were recruited. Nine men had T1c, 4 had T2a, and 3 had T2b and T2c clinical stage. Toxicities included urinary tract infection (n = 3), flu-like syndrome (n = 3), fever (n = 1), dysuria (n = 1), and photophobia (n = 1). Laboratory toxicities were grade 1 elevated AST/ALT (n = 1) and elevations of PTT (n = 3, with 1 proven to be lupus anticoagulant). No pathologic complete remission was seen. Morphologic cytotoxic activity, induction of apoptosis, and nuclear p27(Kip1) upregulation were observed. Peripheral blood CD8(+), CD4(+), and CD3(+) T-lymphocytes were increased, with upregulation of their HLA-DR expression and elevations of serum IL-12.

Conclusions: The intraprostatic administration of GLIPR1 tumor suppressor gene expressed by an adenoviral vector was safe in men, with localized intermediate or high-risk prostate cancer preceding RP. Preliminary evidence of biologic antitumor activity and systemic immune response was documented.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics
  • Aged
  • Gene Transfer Techniques
  • Genes, Suppressor*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Prostatectomy
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Prostatic Neoplasms / therapy*
  • Risk


  • GLIPR1 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins