Submitted July 10, 2006
Accepted November 8, 2006
A neoepitope generated by a FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells
Claudine Graf, Florian Heidel, Stefan Tenzer, Markus P. Radsak, Fian K. Solem, Cedrik M. Britten, Christoph Huber, Thomas Fischer, and Thomas Wolfel*
III. Medizinische Klinik, Johannes Gutenberg-Universitat, Germany
Institut fur Immunologie, Johannes Gutenberg-Universitat, Germany
* Corresponding author; email: t.woelfel{at}3-med.klinik.uni-mainz.de.
The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I-restricted, immunogenic peptides. One of the tested peptides (YVDFREYEYY) induced in vitro autologous T-cell responses restricted by HLA-A*0101, that were also detectable ex vivo. These peptide-reactive T cells recognized targets transfected with the patient's FLT3-ITD, but not wild-type FLT3, and recognized the patient's AML cells. Our results demonstrate that AML leukemic blasts can in principal process and present immunogenic FLT3-ITD neoepitopes. Therefore, FLT3-ITD represents a potential candidate target antigen for the immunotherapy of AML.
