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High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals.
Prostate. 2009 Jan 01; 69(1):70-81.P

Abstract

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.

Authors+Show Affiliations

Clinical Immunology Division, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18814178

Citation

Forsberg, Ole, et al. "High Frequency of Prostate Antigen-directed T Cells in Cancer Patients Compared to Healthy Age-matched Individuals." The Prostate, vol. 69, no. 1, 2009, pp. 70-81.
Forsberg O, Carlsson B, Malmström PU, et al. High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals. Prostate. 2009;69(1):70-81.
Forsberg, O., Carlsson, B., Malmström, P. U., Ullenhag, G., Tötterman, T. H., & Essand, M. (2009). High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals. The Prostate, 69(1), 70-81. https://doi.org/10.1002/pros.20858
Forsberg O, et al. High Frequency of Prostate Antigen-directed T Cells in Cancer Patients Compared to Healthy Age-matched Individuals. Prostate. 2009 Jan 1;69(1):70-81. PubMed PMID: 18814178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals. AU - Forsberg,Ole, AU - Carlsson,Björn, AU - Malmström,Per-Uno, AU - Ullenhag,Gustav, AU - Tötterman,Thomas H, AU - Essand,Magnus, PY - 2008/9/25/pubmed PY - 2009/1/1/medline PY - 2008/9/25/entrez SP - 70 EP - 81 JF - The Prostate JO - Prostate VL - 69 IS - 1 N2 - 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. SN - 1097-0045 UR - https://www.unboundmedicine.com/medline/citation/18814178/High_frequency_of_prostate_antigen_directed_T_cells_in_cancer_patients_compared_to_healthy_age_matched_individuals_ L2 - https://doi.org/10.1002/pros.20858 DB - PRIME DP - Unbound Medicine ER -