Safety and Immunological Efficacy of a DNA Vaccine Encoding Prostatic Acid Phosphatase in Patients With Stage D0 Prostate Cancer

Genitourinary Cancer
Purpose: Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer.

Patients and Methods Twenty-two patients were treated in a dose-escalation trial with 100 µg, 500 µg, or 1,500 µg plasmid DNA, coadministered intradermally with 200 µg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment.

Results: No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFN-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054).

Conclusion: The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.

Supported by Grant No. K23 RR16489 from the National Institutes of Health (NIH; D.G.M., E.J.D.), by a production grant from the NIH National Gene Vector Laboratory Program, by the NIH National Center for Research Resources Clinical and Translational Science Award program (1UL1RR025011), and Grant No. W81XWH-05-1-0404 from the US Army Medical Research and Materiel Command Prostate Cancer Research Program (D.G.M., E.J.D., J.G.D., D.L.H., J.C.E.).


C. G. Drake
Immunotherapy for Prostate Cancer: Walk, Don't Run
J. Clin. Oncol., September 1, 2009; 27(25): 4035 - 4037.

Glycomic characterization of prostate-specific antigen and prostatic acid phosphatase in prostate cancer and benign disease seminal plasma fluids

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are glycoproteins secreted by prostate epithelial cells, and have a long clinical history of use as serum biomarkers of prostate cancers.

These two proteins are present at significantly higher concentrations in seminal plasma, making this proximal fluid of the prostate a good source for purifying enough protein for characterization of prostate disease associated changes in glycan structures. With the use of seminal fluid samples representative of normal control, benign prostatic disease and prostate cancers, PAP and PSA were enriched by thiophilic absorption chromatography.

Released N-linked glycan constituents from both proteins were analyzed by a combination of normal phase HPLC and MALDI-TOF spectrometry. For PSA, 40 putative glycoforms were determined, and 21 glycoforms were determined for PAP. PAP glycans were further analyzed with a hybrid triple quadrupole/linear ion trap mass spectrometer to assign specific glycoform classes to each of the three N-linked sites. The glycans identified in these studies will allow for more defined targeting of prostate disease-specific changes for PAP, PSA and other secreted prostatic glycoproteins.

White KY, Rodemich L, Nyalwidhe JO, Comunale MA, Clements MA, Lance RS, Schellhammer PF, Mehta AS, Semmes OJ, Drake RR.
Department of Microbiology, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA

Prostatic acid phosphatase, a neglected ectonucleotidase.

Two recent papers reveal that the soluble and secreted prostatic acid phosphatase, an enzyme that has long served as a diagnostic marker for prostate cancer, has a membrane-bound splice variant. This enzyme exhibits ecto-5'-nucleotidase activity, is widely distributed, and implicated in the formation of chronic pain.

While prostatic acid phosphatase hydrolyzes phosphomonoesters other than 5'-nucleoside monophosphates these novel data suggest that, in addition to ecto-5'-nucleotidase and the alkaline phosphatases, prostatic acid phosphatase must be taken into account in future studies on extracellular adenosine production.

Institute of Cell Biology and Neuroscience, Biocenter, Goethe-University, 60438, Frankfurt, Germany,

Acid Phospatase

Acid phosphatase is a phosphatase, a type of enzyme, used to free attached phosphate groups from other molecules during digestion. Acid Phosphatase is basically a phospho homo esterase . Acid Phosphatase is stored in lysosomes and functions when these fuse with endosomes, which are acidified while they function; therefore, it has an acid pH optimum.

Different forms of acid phosphatase are found in different organs, and their serum levels are used as a diagnostic for disease in the corresponding organs. For example, elevated prostatic acid phosphatase levels may indicate the presence of prostate cancer.

Prostatic acid phosphatase (PAP) is an enzyme produced by the prostate. Acid phosphatase may be found in increased amounts in men who have prostate cancer or other diseases.

The highest levels of acid phosphatase are found in metastasized prostate cancer. Diseases of the bone, such as Paget's disease or hyperparathyroidism, diseases of blood cells, such as sickle-cell disease or multiple myeloma or lysosomal storage diseases, such as Gaucher's disease, will show moderately increased levels.