Identification of rat prostatic steroid-binding protein as a target antigen of experimental autoimmune prostatitis: implications for prostate cancer therapy.
The long term goal of this study is to develop autoimmune prostatitis as a therapy for prostate cancer. An immune attack capable of destroying normal prostate epithelial cells should also destroy malignant prostate tissue and provide therapeutic benefit in cancer patients. The current study was initiated to identify antigenic targets for experimental autoimmune prostatitis on the assumption that such proteins might also be suitable targets for immunotherapy of prostate cancer. Male Lewis rats were immunized with syngeneic prostate homogenates, and the immune sera were used to screen prostate proteins for immunoreactivity by Western blot analysis. The dominant protein recognized by the immune sera was purified by ion exchange chromatography and reverse phase HPLC. Microsequence analysis of two polypeptide components of this immunodominant protein demonstrated N-terminal sequences identical with two of the three component chains of rat prostatic steroid-binding protein (PSBP). T cell responses to PSBP were also detected in rats immunized with prostate homogenate. Immunizing male rats with purified PSBP induced vigorous Ab and T cell responses. Significant prostate inflammation was observed in some rats immunized with PSBP. Adoptive transfer of T cells immune to PSBP induced rapid and severe destructive autoimmune prostatitis. These results demonstrate that PSBP is a major target Ag of experimental autoimmune prostatitis in a rat model and may serve as a target Ag for vaccine and T cell therapy against prostate cancer.
Liu
K J
KJ
Department of Medicine, University of Washington, Seattle 98195, USA.
Chatta
G S
GS
Twardzik
D R
DR
Vedvick
T S
TS
True
L D
LD
Spies
A G
AG
Cheever
M A
MA
D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D007114:Immunization; D007167:Immunotherapy; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy; D011472:Prostatitis / Q000276:immunology*; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013256:Steroids / Q000378:metabolism*
D001324:Autoantigens; D011506:Proteins; D013256:Steroids