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Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation

Authors :
Samuel Strober
Antonia M.S. Müller
Evan W. Newell
Jeanette Baker
Suparna Dutt
Holbrook E Kohrt
Robert Lowsky
Debra K. Czerwinski
Matthew J. Goldstein
Source :
Blood. 118(19)
Publication Year :
2011

Abstract

Abstract 1896 The curative potential of MHC-matched allogeneic bone marrow transplantation (BMT) is in part due to immunologic graft-versus-tumor (GvT) reactions mediated by donor T cells that recognize host minor histocompatibility antigens. Immunization with leukemia-associated antigens, such as Wilm's Tumor 1 (WT1) peptides, induces a T cell population that is tumor antigen specific. We determined whether BMT combined with immunotherapy using WT1 peptide vaccination of donors induced more potent anti-tumor activity when combined with allotransplantation. WT1 peptide vaccinations of healthy syngeneic or allogeneic donor mice with a 9-mer WT1 peptide (amino acids 126–134, the WT1 9-mer which has the highest binding affinity for H-2Db) and Incomplete Freund's Adjuvant induced CD8+ T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells. We found that compared to vaccination with IFA alone, four weekly WT1 vaccinations induced an increased percentage of WT1-tetramer+CD8 T-cells (0.15% vs. 1%) in the peripheral blood 28 days following the first vaccination (Figure A *p Disclosures: No relevant conflicts of interest to declare.

Details

ISSN :
15280020
Volume :
118
Issue :
19
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....05975ec4445e182fd7d4b273609ecd1b