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Identification of prostate infiltrating lymphocytes and activation of prostate antigen-specific T cells isolated from prostate cancer patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Gen och immunoterapigruppen)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Gen och immunoterapigruppen)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Gen och immunoterapigruppen)
(English)Manuscript (Other academic)
Abstract [en]

Although prostate antigen-specific CD8+ T lymphocytes have been found both in peripheral blood and in tumor area of prostate cancer patients there has not yet been any adequate adoptive T lymphocyte transfer trial for prostate cancer patients. Methods for efficient generation of large number of prostate antigen-specific T cells are still lacking. In the present study we isolate and expand prostate infiltrating lymphocytes (PILs) from resected prostates by fine needle aspiration of patients with localized prostate cancer. By using HLA-A*0201-restricted tetramers, specific for the prostate tumor-associated antigen epitopes TARP(P5L)4-13, STEAP262-270 and PSA53-61, we were able to identify prostate antigen-specific CD8+ PILs in 5 out of 5 patients. Most frequent were STEAP262-270-specific T cells (5/5). Furthermore, by using fast-matured dendritic cells (DCs) transduced with an adenoviral vector encoding the STEAP antigen we were able to generate CD8+ T cells from peripheral blood of prostate cancer patients, for three HLA-A*0201-restricted STEAP epitopes simultaneously by one stimulation only. If combined, an effective protocol for generation of prostate antigen-specific T cells may be developed.

National Category
Immunology in the medical area
Research subject
Clinical Immunology
Identifiers
URN: urn:nbn:se:uu:diva-100510OAI: oai:DiVA.org:uu-100510DiVA: diva2:210410
Available from: 2009-04-07 Created: 2009-04-01 Last updated: 2010-01-14Bibliographically approved
In thesis
1. Generation of Therapeutic T Cells for Prostate Cancer
Open this publication in new window or tab >>Generation of Therapeutic T Cells for Prostate Cancer
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The work presented herein focuses on the activation of the adaptive immune system in order to develop T cell-based immunotherapy for viral infections and cancer. The main goal was to identify and activate viral or tumoral antigen-specific T cells by using different identification, isolation and stimulation techniques. One such approach was that we modified dendritic cells (DCs) with an adenoviral vector encoding the full length pp65 antigen from cytomegalovirus (CMV). Through strategic modification techniques we demonstrate that it is possible to obtain DCs presenting antigen-specific peptides both on major histocompatibility complex (MHC) class I and MHC class II molecules for simultaneous CD8+ and CD4+ T cell activation. We also demonstrate that it is possible to generate prostate antigen-specific CD8+ T cells from a naïve repertoire of T cells by using DCs and HLA-A2-restricted peptides derived from prostate tumor-associated antigens or by using an adenoviral vector encoding the full length prostate tumor-associated antigen STEAP. We further demonstrate that CD8+ T cells directed against several prostate-specific peptide epitopes can be found in peripheral blood and in the prostate tumor area of prostate cancer patients. Furthermore, we have characterized a number of prostate-derived cell lines in terms of HLA haplotype and tumor-association antigen expression. We concluded that our methods for generating T cells restricted to CMV antigen have the ability to be applied for adoptive T cell transfer to patients with CMV disease and that prostate antigen-specific T cells can be found within prostate cancer patients, which enables future development of immunotherapeutic strategies for prostate cancer.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 447
Keyword
Prostate cancer, T cells, dendritic cells, peptides, cytomegalovirus, adenovirus, immunotherapy
National Category
Immunology in the medical area
Research subject
Clinical Immunology
Identifiers
urn:nbn:se:uu:diva-100506 (URN)978-91-554-7491-1 (ISBN)
Public defence
2009-05-26, Rudbecksalen, Rudbecklaboratoriet C11, Dag Hammarskjölds väg 20, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2009-05-05 Created: 2009-04-01 Last updated: 2010-04-29Bibliographically approved

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Forsberg, Ole

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