A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols

Publikation: Beiträge in ZeitschriftenZeitschriftenaufsätzeForschungbegutachtet

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A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols. / Lundberg, Kajsa; Roos, Anna-Karin ; Pavlenko, Maxim et al.
in: Vaccine, Jahrgang 27, Nr. 10, 04.03.2009, S. 1557-1565.

Publikation: Beiträge in ZeitschriftenZeitschriftenaufsätzeForschungbegutachtet

Harvard

Lundberg, K, Roos, A-K, Pavlenko, M, Leder, C, Wehrum, D, Guevara-Patiño, J, Andersen, RS & Pisa, P 2009, 'A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols', Vaccine, Jg. 27, Nr. 10, S. 1557-1565. https://doi.org/10.1016/j.vaccine.2009.01.011

APA

Lundberg, K., Roos, A.-K., Pavlenko, M., Leder, C., Wehrum, D., Guevara-Patiño, J., Andersen, R. S., & Pisa, P. (2009). A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols. Vaccine, 27(10), 1557-1565. https://doi.org/10.1016/j.vaccine.2009.01.011

Vancouver

Lundberg K, Roos AK, Pavlenko M, Leder C, Wehrum D, Guevara-Patiño J et al. A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols. Vaccine. 2009 Mär 4;27(10):1557-1565. doi: 10.1016/j.vaccine.2009.01.011

Bibtex

@article{747affdc11e0426ea431c945a4303f60,
title = "A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols",
abstract = "Efficacy of vaccination in cancer patients on immunotherapeutic protocols can be difficult to evaluate. The aim of this study was therefore to identify a single natural or modified epitope in prostate-specific antigen (PSA) with the ability to generate high levels of PSA-specific T cells to facilitate monitoring in patients after vaccination against prostate cancer. To the best of our knowledge, this study describes for the first time the peptide specificity of T cells stimulated by endogenously processed PSA antigen. The peptide specificity of HLA-A*0201-restricted CD8+ T cells against human and rhesus PSA was investigated both in vivo after DNA vaccination in HLA-A*0201-transgenic mice and in vitro after repetitive stimulation of human T cells with DNA-transfected human dendritic cells (DCs). One of seven native PSA peptides, psa53–61, was able to activate high levels of PSA-specific CD8+ T cells in HLA-A*0201-transgenic mice after PSA DNA vaccination. Psa53–61 was also the only peptide that induced human T cells to produce IFNγ after stimulation with PSA transfected DCs, however not in all donors. Therefore, plasmids encoding modified epitopes in predicted HLA-A*0201 sequences were constructed. One of these modified PSA plasmids consistently induced IFNγ producing CD8+ T cells to the corresponding modified peptide as well as to the corresponding native peptide, in all murine and human T cell cultures. This study demonstrates a novel concept of introducing a modified epitope within a self-tumor antigen, with the purpose of eliciting a reliable T cell response from the non-tolerized immune repertoire, to facilitate monitoring of vaccine efficacy in cancer patients on immunotherapeutic protocols. The purpose of such a modified epitope is thus not to induce therapeutically relevant T cells but rather to, in case of weak or divergent T cell responses to self antigens/peptides, help answer questions about efficacy of vaccine delivery and about the possibility to induce immune responses in the selected and often immunosuppressed cancer patients.",
keywords = "Health sciences, T cells, Peptides, Vaccination, Prostate-specific antigen, Monitoring, Monitoring, Peptides, Prostate-specific antigen, T cells, Vaccination",
author = "Kajsa Lundberg and Anna-Karin Roos and Maxim Pavlenko and Christoph Leder and Diana Wehrum and Jos{\'e} Guevara-Pati{\~n}o and Andersen, {Rikke Sick} and Pavel Pisa",
year = "2009",
month = mar,
day = "4",
doi = "10.1016/j.vaccine.2009.01.011",
language = "English",
volume = "27",
pages = "1557--1565",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier B.V.",
number = "10",

}

RIS

TY - JOUR

T1 - A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols

AU - Lundberg, Kajsa

AU - Roos, Anna-Karin

AU - Pavlenko, Maxim

AU - Leder, Christoph

AU - Wehrum, Diana

AU - Guevara-Patiño, José

AU - Andersen, Rikke Sick

AU - Pisa, Pavel

PY - 2009/3/4

Y1 - 2009/3/4

N2 - Efficacy of vaccination in cancer patients on immunotherapeutic protocols can be difficult to evaluate. The aim of this study was therefore to identify a single natural or modified epitope in prostate-specific antigen (PSA) with the ability to generate high levels of PSA-specific T cells to facilitate monitoring in patients after vaccination against prostate cancer. To the best of our knowledge, this study describes for the first time the peptide specificity of T cells stimulated by endogenously processed PSA antigen. The peptide specificity of HLA-A*0201-restricted CD8+ T cells against human and rhesus PSA was investigated both in vivo after DNA vaccination in HLA-A*0201-transgenic mice and in vitro after repetitive stimulation of human T cells with DNA-transfected human dendritic cells (DCs). One of seven native PSA peptides, psa53–61, was able to activate high levels of PSA-specific CD8+ T cells in HLA-A*0201-transgenic mice after PSA DNA vaccination. Psa53–61 was also the only peptide that induced human T cells to produce IFNγ after stimulation with PSA transfected DCs, however not in all donors. Therefore, plasmids encoding modified epitopes in predicted HLA-A*0201 sequences were constructed. One of these modified PSA plasmids consistently induced IFNγ producing CD8+ T cells to the corresponding modified peptide as well as to the corresponding native peptide, in all murine and human T cell cultures. This study demonstrates a novel concept of introducing a modified epitope within a self-tumor antigen, with the purpose of eliciting a reliable T cell response from the non-tolerized immune repertoire, to facilitate monitoring of vaccine efficacy in cancer patients on immunotherapeutic protocols. The purpose of such a modified epitope is thus not to induce therapeutically relevant T cells but rather to, in case of weak or divergent T cell responses to self antigens/peptides, help answer questions about efficacy of vaccine delivery and about the possibility to induce immune responses in the selected and often immunosuppressed cancer patients.

AB - Efficacy of vaccination in cancer patients on immunotherapeutic protocols can be difficult to evaluate. The aim of this study was therefore to identify a single natural or modified epitope in prostate-specific antigen (PSA) with the ability to generate high levels of PSA-specific T cells to facilitate monitoring in patients after vaccination against prostate cancer. To the best of our knowledge, this study describes for the first time the peptide specificity of T cells stimulated by endogenously processed PSA antigen. The peptide specificity of HLA-A*0201-restricted CD8+ T cells against human and rhesus PSA was investigated both in vivo after DNA vaccination in HLA-A*0201-transgenic mice and in vitro after repetitive stimulation of human T cells with DNA-transfected human dendritic cells (DCs). One of seven native PSA peptides, psa53–61, was able to activate high levels of PSA-specific CD8+ T cells in HLA-A*0201-transgenic mice after PSA DNA vaccination. Psa53–61 was also the only peptide that induced human T cells to produce IFNγ after stimulation with PSA transfected DCs, however not in all donors. Therefore, plasmids encoding modified epitopes in predicted HLA-A*0201 sequences were constructed. One of these modified PSA plasmids consistently induced IFNγ producing CD8+ T cells to the corresponding modified peptide as well as to the corresponding native peptide, in all murine and human T cell cultures. This study demonstrates a novel concept of introducing a modified epitope within a self-tumor antigen, with the purpose of eliciting a reliable T cell response from the non-tolerized immune repertoire, to facilitate monitoring of vaccine efficacy in cancer patients on immunotherapeutic protocols. The purpose of such a modified epitope is thus not to induce therapeutically relevant T cells but rather to, in case of weak or divergent T cell responses to self antigens/peptides, help answer questions about efficacy of vaccine delivery and about the possibility to induce immune responses in the selected and often immunosuppressed cancer patients.

KW - Health sciences

KW - T cells

KW - Peptides

KW - Vaccination

KW - Prostate-specific antigen

KW - Monitoring

KW - Monitoring

KW - Peptides

KW - Prostate-specific antigen

KW - T cells

KW - Vaccination

UR - http://www.scopus.com/inward/record.url?scp=60649083935&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2009.01.011

DO - 10.1016/j.vaccine.2009.01.011

M3 - Journal articles

C2 - 19171173

VL - 27

SP - 1557

EP - 1565

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 10

ER -

DOI