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A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells.
- Source :
-
Blood [Blood] 2007 Apr 01; Vol. 109 (7), pp. 2985-8. - Publication Year :
- 2007
-
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.
- Subjects :
- Amino Acid Sequence
Antigen Presentation
Cell Line
Cell Line, Tumor
Epitopes genetics
HLA-A Antigens genetics
HLA-A Antigens metabolism
HLA-A1 Antigen
Humans
In Vitro Techniques
Leukemia, Myeloid, Acute enzymology
Molecular Sequence Data
RNA, Messenger genetics
Transfection
CD8-Positive T-Lymphocytes immunology
Gene Duplication
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute immunology
fms-Like Tyrosine Kinase 3 genetics
fms-Like Tyrosine Kinase 3 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 109
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 17119119
- Full Text :
- https://doi.org/10.1182/blood-2006-07-032839