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

Guru Sonpavde, Timothy C. Thompson, Rajul K. Jain, Gustavo E. Ayala, Shinji Kurosaka, Kohei Edamura, Ken Ichi Tabata, Chengzhen Ren, Alexei A. Goltsov, Martha P. Mims, Teresa G. Hayes, Michael M. Ittmann, Thomas M. Wheeler, Adrian Gee, Brian J. Miles, Dov Kadmon

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 Kip1upregulation 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.

Original languageEnglish
Pages (from-to)7174-7182
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number22
DOIs
Publication statusPublished - Nov 15 2011
Externally publishedYes

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Prostatectomy
Tumor Suppressor Genes
Prostatic Neoplasms
Injections
Virion
Dysuria
Lupus Coagulation Inhibitor
Photophobia
Clinical Trials, Phase I
Neoplasm Grading
HLA-DR Antigens
Interleukin-12
Prostate-Specific Antigen
Adenoviridae
Urinary Tract Infections
Prostate
Fever
Up-Regulation
Apoptosis
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

GLIPR1 tumor suppressor gene expressed by adenoviral vector as neoadjuvant intraprostatic injection for localized intermediate or high-risk prostate cancer preceding radical prostatectomy. / Sonpavde, Guru; Thompson, Timothy C.; Jain, Rajul K.; Ayala, Gustavo E.; Kurosaka, Shinji; Edamura, Kohei; Tabata, Ken Ichi; Ren, Chengzhen; Goltsov, Alexei A.; Mims, Martha P.; Hayes, Teresa G.; Ittmann, Michael M.; Wheeler, Thomas M.; Gee, Adrian; Miles, Brian J.; Kadmon, Dov.

In: Clinical Cancer Research, Vol. 17, No. 22, 15.11.2011, p. 7174-7182.

Research output: Contribution to journalArticle

Sonpavde, G, Thompson, TC, Jain, RK, Ayala, GE, Kurosaka, S, Edamura, K, Tabata, KI, Ren, C, Goltsov, AA, Mims, MP, Hayes, TG, Ittmann, MM, Wheeler, TM, Gee, A, Miles, BJ & Kadmon, D 2011, 'GLIPR1 tumor suppressor gene expressed by adenoviral vector as neoadjuvant intraprostatic injection for localized intermediate or high-risk prostate cancer preceding radical prostatectomy', Clinical Cancer Research, vol. 17, no. 22, pp. 7174-7182. https://doi.org/10.1158/1078-0432.CCR-11-1899
Sonpavde, Guru ; Thompson, Timothy C. ; Jain, Rajul K. ; Ayala, Gustavo E. ; Kurosaka, Shinji ; Edamura, Kohei ; Tabata, Ken Ichi ; Ren, Chengzhen ; Goltsov, Alexei A. ; Mims, Martha P. ; Hayes, Teresa G. ; Ittmann, Michael M. ; Wheeler, Thomas M. ; Gee, Adrian ; Miles, Brian J. ; Kadmon, Dov. / GLIPR1 tumor suppressor gene expressed by adenoviral vector as neoadjuvant intraprostatic injection for localized intermediate or high-risk prostate cancer preceding radical prostatectomy. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 22. pp. 7174-7182.
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abstract = "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 Kip1upregulation 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.",
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AU - Thompson, Timothy C.

AU - Jain, Rajul K.

AU - Ayala, Gustavo E.

AU - Kurosaka, Shinji

AU - Edamura, Kohei

AU - Tabata, Ken Ichi

AU - Ren, Chengzhen

AU - Goltsov, Alexei A.

AU - Mims, Martha P.

AU - Hayes, Teresa G.

AU - Ittmann, Michael M.

AU - Wheeler, Thomas M.

AU - Gee, Adrian

AU - Miles, Brian J.

AU - Kadmon, Dov

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N2 - 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 Kip1upregulation 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.

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