title: Increased frequency and responsiveness of PSA-specific T cells after allogeneic hematopoetic stem-cell transplantation.
abstract: BACKGROUND
  Therapies for localized prostate cancer include curative surgery and radiotherapy while treatment of metastatic disease is often inefficient. Graft-versus-tumor effects of allogeneic stem-cell transplantation (ASCT) have been described for several types of solid tumors but have not been reported for prostate cancer. We, therefore, investigated the potential of ASCT as treatment for noncurable prostate cancer.
  
  
  METHODS
  A patient underwent ASCT from his human leukocyte antigen (HLA)-identical sister as treatment for his metastatic prostate adenocarcinoma. Frequencies of prostate-specific T cells in the peripheral blood of the patient, ASCT donor and a group of control individuals were determined by flow cytometry using pentameric HLA-A2 complexes containing peptides derived from the prostate-specific antigen (PSA). Cytotoxic activity of PSA-peptide-specific T cells against peptide-pulsed target cells was analyzed ex vivo by Cr-release assays.
  
  
  RESULTS
  Stable clinical and laboratory remission lasting more than 4 years was observed after ASCT. Using HLA-containing pentamers with PSA-derived peptides we could detect prostate-specific CD8+ T cells in this patient at high frequencies over several months. Furthermore, higher frequencies of PSA-specific T cells were revealed in the blood of the patient and female controls when compared with healthy males.
  
  
  CONCLUSIONS
  Lymphocytes from the peripheral blood of the recipient, but not from donor or other tested control individuals, exhibited ex vivo cytotoxic activity against target cells pulsed with the relevant synthetic peptides and efficiently expanded in vitro following specific restimulations. Thus, the results of this study indicate that female to male ASCT can increase the frequency and enhance specific-responsiveness of PSA-specific T cells in transplant recipients.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation and Division of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden. michael.uhlin@ki.se
authors.forename: Michael
authors.initials: M
authors.lastname: Uhlin
authors.forename: Mantas
authors.initials: M
authors.lastname: Okas
authors.forename: Helen
authors.initials: H
authors.lastname: Karlsson
authors.forename: Jens
authors.initials: J
authors.lastname: Gertow
authors.forename: Lars
authors.initials: L
authors.lastname: Henningsohn
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.forename: Victor
authors.initials: V
authors.lastname: Levitsky
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000465:Algorithms; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000097:blood; D002470:Cell Survival; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data*; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D000939:Epitopes; D015789:HLA-A2 Antigen; D017430:Prostate-Specific Antigen