Androgen Ablation Augments Prostate Cancer Vaccine Immunogenicity Only When Applied After Immunization

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 14 Feb 2009 - 1:00 PDT

email to a friend   printer friendly   opinions  

UroToday.com - In the online edition of The Prostate, a group of researchers from the Norris Comprehensive Cancer Center at USC reported on the relationship between androgen ablation (AA) and the efficacy of vaccine immunogenicity. In the AA setting, testosterone-mediated immune suppression is reduced and prostate antigens are released. Dendritic cells (DC) are specialized antigen presenting cells that migrate to the periphery to "capture' antigens and process them into polypeptides, migrate into lymphoid organs and present the antigens to lymphocytes. The effect of AA on DC has not previously been reported. In this study, the researchers tested the effect of AA on DC when using prostate stem cell antigen (PSCA), a cell surface protein as a PSCA-targeted vaccination strategy.

The study had two groups of mice, one castrated and one sham-castrated. A multiplex cytokine assay performed 3 weeks after surgery found the immunosuppressive protein IL-10 was reduced by AA, and the pro-inflammatory IL-17 and bioactive IL-12p70 were also reduced. IL-1a and IL-12p40 were increased in the sera of castrated mice. IL-6 and TNF- did not differ between castrated and sham-castrated mice. The main hypothesis in the report tested whether the increase in DC co-stimulation results in functional improvements in T cell responses. DCs from castrated and sham-castrated mice were used in allogeneic mixed leukocyte reactions and a vaccination strategy was tested in combination with AA. They found no functional improvement in the co-stimulation ability of the DC post-AA in either young or middle-aged mice.

To definitively demonstrate the effect of AA on CaP immunotherapy when carried out either before or after PSCA vaccination, mice were subjected to combined castration and vaccination protocols. Castration alone induced a PSCA-specific response, suggesting that AA led to apoptosis of androgen-dependent prostate cells that expressed PSCA resulting in the development of a PSCA-specific response. When vaccination took place prior to AA, mice had slightly increased numbers of PSCA-specific IFN secreting cells compared to vaccinated mice that were sham-castrated. When the treatment order was reversed and castration took place before vaccination, AA did not lead to an increase in PSCA-specific IFN secreting cells when compared to mice that were sham-castrated and underwent vaccination. The castration-induced reaction against PSCA was not detected when AA was carried out prior to vaccination.

Koh YT, Gray A, Higgins SA, Hubby B, Kast WM
Prostate. 2009 Jan 13. (Epub ahead of print)
doi: 10.1002/pros.20906

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

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to: www.urotoday.com

Copyright © 2009 - UroToday

• Additional
• References
• Citations