BACKGROUND. In order to obtain a sustained cytotoxic T lymphocyte (CTL) response against cancer cells it is preferable to have CTLs directed against multiple peptide epitopes from numerous tumor-associated antigens. METHODS. We used a Flow Cytometry-based interferon (IFN)-g secretion assay with peptide-pulsed C1R-A2 as antigen-presenting cells to analyze whether CD8 þ T cells directed against any of 24 HLA-A*0201-binding peptides from 15 prostate-associated proteins can be found in the peripheral blood of patients with localized prostate cancer. We also investigated whether multiple prostate antigen-specific CD8 þ T cells can be generated simultaneously, from a naïve T cell repertoire. In that case, dendritic cells (DCs) from peripheral blood of healthy donors were divided in six portions and separately pulsed with six peptides. The peptide-pulsed DCs were then pooled and used to stimulate autologous T cells. The T cells were re-stimulated with peptide-pulsed monocytes. RESULTS. We found prostate antigen-restricted CD8 þ T cells in the peripheral blood in 48 out of 184 (26.1%) analyzed samples from 25 cancer patients. This is significantly higher than 17 out of 214 analyzed samples (7.9%) from 10 healthy age-matched male individuals (P ¼ 0.0249). In the cases when antigen-specific T cells could not be detected, we were able to generate IFN-gproducing CD8þ T cells specific for up to three prostate antigens simultaneously from a naïve T cell repertoire.
CONCLUSIONS. CD8þ T cells directed against prostate antigen peptides can be found in, or generated from, peripheral blood. This indicates that such T cells could be expanded ex vivo for adoptive transfer to prostate cancer patients.
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