Prostatic acid phosphatase expression in human tissues

Introduction: Active cellular immunotherapy seeks to induce tumor-specific immunity in the patient and is consequently dependent on a suitable target tumor antigen. Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP), and has demonstrated evidence of survival prolongation in men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer in randomized clinical trials. PAP has been tested as a target antigen due to its high, and relatively specific, expression in the prostate. PAP expression in other human tissues was examined to help anticipate potential safety concerns associated with the development of immunity in this target.

Methods: We used a variety of approaches to analyze PAP expression, including immunohistochemistry, in situ hybridization, and quantitative polymerase chain reaction. These laboratory-based techniques were complemented with an in silico analysis of reported PAP expression in human cDNA libraries.

Results: Our studies confirmed that, while PAP expression is not restricted to prostate tissues, its expression in other human tissues is approx. 1 to 2 orders of magnitude less than that observed in the prostate.

Conclusion: The relative specificity of PAP expression in prostate tissues supports its use in immunotherapies targeting prostate carcinoma. A greater knowledge of the expression of immunotherapy targets through a range of human cancers will better define appropriate clinical settings for their use; detailed assessment of their normal tissue distribution will aid the design of future clinical protocols for monitoring the safety of these potential therapeutic regimens.