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Blood, 1 January 2008, Vol. 111, No. 1, pp. 236-242.
Prepublished online as a Blood First Edition Paper on September 17, 2007; DOI 10.1182/blood-2007-08-108241.
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Submitted August 20, 2007
Accepted September 13, 2007
Leukemia-associated antigen specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies
Katayoun Rezvani*, Agnes SM Yong, Stephan Mielke, Bipin N Savani, Laura Musse, Jeanine Superata, Behnam Jafarpour, Carol Boss, and A John Barrett
Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: rezvanik{at}nhlbi.nih.gov.
We describe the safety and immunogenicity of a combined vaccine of two 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 immunological responses. Toxicity was limited to grade 1-2. Using peptide/HLA-A*0201 tetramers and intracellular interferon- staining, CD8+ T-cells against PR1 or WT1 were detected in 8/8 patients after a single vaccination. To monitor the kinetics of vaccine-induced CD8+ T-cell responses and disease regression post-vaccination, absolute PR1 and WT1+CD8+ T-cell numbers and WT1 expression were studied weekly post-vaccination. Responses occurred as early as 1 week post-vaccination. Post-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 anti-leukemia effect. Conversely, loss of response was associated with reappearance of WT1 transcripts (P<0.01). 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.

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