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Blood. 2008 Jan 1;111(1):236-42. Epub 2007 Sep 17.

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

Author information

1
Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1201, USA. rezvanik@nhlbi.nih.gov

Abstract

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-gamma 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00313638.

PMID:
17875804
PMCID:
PMC2200809
DOI:
10.1182/blood-2007-08-108241
[Indexed for MEDLINE]
Free PMC Article

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