A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells

Blood. 2007 Apr 1;109(7):2985-8. doi: 10.1182/blood-2006-07-032839.

Abstract

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 principle process and present immunogenic FLT3-ITD neoepitopes. Therefore, FLT3-ITD represents a potential candidate target antigen for the immunotherapy of AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cell Line, Tumor
  • Epitopes / genetics
  • Gene Duplication*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / metabolism
  • HLA-A1 Antigen
  • Humans
  • In Vitro Techniques
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / immunology*
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • Transfection
  • fms-Like Tyrosine Kinase 3 / genetics*
  • fms-Like Tyrosine Kinase 3 / immunology*

Substances

  • Epitopes
  • HLA-A Antigens
  • HLA-A*01:01 antigen
  • HLA-A1 Antigen
  • RNA, Messenger
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3