Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies

DOI PDF 被引用文献20件
  • Katayoun Rezvani
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • Agnes S. M. Yong
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • Stephan Mielke
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • Bipin N. Savani
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • Laura Musse
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • Jeanine Superata
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • Behnam Jafarpour
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • Carol Boss
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • A. John Barrett
    Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

書誌事項

公開日
2008-01-01
DOI
  • 10.1182/blood-2007-08-108241
公開者
American Society of Hematology

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説明

<jats:p>We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1. Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor. Patients were reviewed weekly for 4 weeks to monitor toxicity and immunologic responses. Toxicity was limited to grades 1 to 2. Using peptide/HLA-A*0201 tetramers and intracellular interferon-γ staining, CD8+ T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination. To monitor the kinetics of vaccine-induced CD8+ T-cell responses and disease regression after vaccination, absolute PR1 and WT1+CD8+ T-cell numbers and WT1 expression were studied weekly after vaccination. Responses occurred as early as 1 week after vaccination. After vaccination, the emergence of PR1 or WT1+CD8+ T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect. Conversely, loss of response was associated with reappearance of WT1 transcripts (P < .01). This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic. These results support further studies of combination immunization strategies in leukemia patients. This study is registered at http://clinicaltrials.gov as NCT00313638.</jats:p>

収録刊行物

  • Blood

    Blood 111 (1), 236-242, 2008-01-01

    American Society of Hematology

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