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)-gamma secretion assay with peptide-pulsed C1R-A2 as antigen-presenting cells to analyze whether CD8+ 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+ 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+ 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 = 0.0249). In the cases when antigen-specific T cells could not be detected, we were able to generate IFN-gamma-producing CD8+ T cells specific for up to three prostate antigens simultaneously from a naïve T cell repertoire. CONCLUSIONS: CD8+ 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. Copyright 2008 Wiley-Liss, Inc.
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)-gamma secretion assay with peptide-pulsed C1R-A2 as antigen-presenting cells to analyze whether CD8+ 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+ 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+ T cells in the peripheral blood in 48 out of 184 (26.1%) analyzed samples from 25 cancerpatients. This is significantly higher than 17 out of 214 analyzed samples (7.9%) from 10 healthy age-matched male individuals (P = 0.0249). In the cases when antigen-specific T cells could not be detected, we were able to generate IFN-gamma-producing CD8+ T cells specific for up to three prostate antigens simultaneously from a naïve T cell repertoire. CONCLUSIONS: CD8+ 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 cancerpatients. Copyright 2008 Wiley-Liss, Inc.
Authors: Victoria Hillerdal; Berith Nilsson; Björn Carlsson; Fredrik Eriksson; Magnus Essand Journal: Proc Natl Acad Sci U S A Date: 2012-09-10 Impact factor: 11.205
Authors: Mathilda Eriksson; Kalle Andreasson; Joachim Weidmann; Kajsa Lundberg; Karin Tegerstedt; Tina Dalianis; Torbjörn Ramqvist Journal: PLoS One Date: 2011-08-17 Impact factor: 3.240