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

Katayoun Rezvani, Agnes S M Yong, Stephan Mielke, Bipin N. Savani, Laura Musse, Jeanine Superata, Behnam Jafarpour, Carol Boss, A. John Barrett

Research output: Contribution to journalArticlepeer-review

292 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalBlood
Volume111
Issue number1
DOIs
Publication statusPublished or Issued - 1 Jan 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this