Safety And Immunological Efficacy Of A DNA Vaccine Encoding Prostatic Acid Phosphatase In Patients With Stage D0 Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 01 Nov 2009 - 3:00 PST

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UroToday.com - In the online edition of the Journal of Clinical Oncology, Dr. Douglas McNeel and associates report a phase I/IIa trial of a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with stage D0 prostate cancer (CaP). PAP is a prostate tumor antigen that can elicit an immunologic antigen-specific CD8+ T cell response. The vaccine, pTVG-HP, is a plasmid DNA encoding the full length human PAP cDNA downstream of a eukaryotic promoter.

Study patients included those with a rising PSA after primary therapy (stage D0). The design was single institution, with a dose escalation; level 1 to 100ug, level 2 to 500ug and level 3 to 1,500ug. Dose-limiting toxicity was defined as adverse events higher than grade 2. The maximum tolerated dose (MTD) was the dose level preceding a level at which more than one DLT was observed, or the 1,500ug level in the absence of DLTs. Patients were treated 6 times at 14-day intervals with the vaccine co-administered with 200ug granulocyte-macrophage colony-stimulating factor. The vaccine was delivered intradermally on the arm in two to three divided administrations. Blood tests including PSA were performed monthly. Autologous antigen-presenting cells were prepared by culturing tissue flask-adherent peripheral blood mononuclear cells (PBMNC) in the presence of 20ng/ml recombinant human granulocyte-macrophage colony-stimulating factor and 10ng/ml recombinant human IL-4 for 6 days. T cells were sorted and cultured with dendritic cells plus PAP protein, PSA protein, and tetanus toxoid. Cells were transferred to immunospot plates coated with anti-IFN capture antibody. T-cell response was determined by BrdU incorporation assay with flow cytometric evaluation.

The patient cohort consisted of 22 men and no adverse events higher than grade 2 occurred, so 9 patients were accrued at the 3 dose escalation levels and an additional 13 men at the 1,500ug dose level. Induction of PAP-specific IFN-secreting CD8+ T cells was the primary response. Three of 22 men had evidence of a response to PAP, one in each treatment dose group. Two of 22 patients had a CD8+ IFN-secreting response to tetanus toxoid. Six of 22 men had a 3-fold or higher increase in CD8+ proliferative T-cells. No patient had either a complete PSA response or a PSA decline greater than 50%. However, the median PSADT increased from 6.5 months pre-treatment to 8.5 months on-treatment to 9.3 months post-treatment.

McNeel DG, Dunphy EJ, Davies JG, Frye TP, Johnson LE, Staab MJ, Horvath DL, Straus J, Alberti D, Marnocha R, Liu G, Eickhoff JC, Wilding G
J Clin Oncol. 2009 Jul 27. Epub ahead of print
doi:10.1200/JCO.2008.19.9968

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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