Identification of naturally processed CD8 T cell epitopes from prostein, a prostate tissue-specific vaccine candidate.
Prostein is a prostate tissue-specific protein that is uniquely and abundantly expressed in normal and cancerous prostate tissues. Due to this expression profile, we examined the immunogenicity of prostein as a potential vaccine candidate for prostate cancer. To determine the presence of CD8 T cells specific for naturally processed prostein-derived epitopes in healthy individuals, we developed and applied an in vitro stimulation protocol. Using this protocol, we identified CD8 T cells specific for prostein in the peripheral blood of a male and a female donor. Prostein-specific CD8 T cell clones specifically recognized prostein-expressing targets, including prostate tumor cell lines expressing the relevant HLA alleles. CD8 T cell clones isolated from the male donor were significantly less effective in recognizing target cells compared to cells isolated from the female donor and appeared to recognize subdominant epitopes. The identification of a prostein-specific CD8 T cell repertoire supports the development of prostein in vaccination strategies against prostate cancer. Furthermore, the naturally processed peptide epitopes identified provide tools for the development of peptide-based vaccination strategies against prostate cancer and for monitoring of prostein-specific responses in vaccinated patients.
Friedman
Rachel S
RS
Corixa Corporation, Seattle, USA.
Spies
A Gregory
AG
Kalos
Michael
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D012737:Sex Factors; D014162:Transfection
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; C422655:prostein