title: "Wilms Tumor Protein 1" (WT1) peptide vaccination-induced complete remission in a patient with acute myeloid leukemia is accompanied by the emergence of a predominant T-cell clone both in blood and bone marrow.
abstract: Within the last few years, the first peptide vaccination trials for treatment of acute myeloid leukemia (AML) have been initiated. Athough the presence of epitope-specific T cells could be seen both in bone marrow (BM) and peripheral blood (PB), nothing is known about their clonal composition. In this study, we analyzed material from a patient with recurrent AML vaccinated with "Wilms Tumor Protein 1" (WT1) peptide, who achieved a complete remission (CR) lasting for 12 months. For identification of expanded WT1-specific T-cell clones, enrichment by tetramer and IFNγ secretion were followed by comparative quantitative reverse transcribed PCR (qRT PCR) quantification of all TCR Vβ-families. Vβ-families with increase in the enriched fraction were cloned and sequenced. A predominant clone was quantified by clonotypic qRT PCR from PB and BM. Quantity and functionality of WT1-specific cells were assessed by tetramer analyses and intracellular IFNγ staining. A specific predominant clone was identified during clinical remission. Clone-specific qRT PCR showed an increase both in PB and BM after 8 vaccinations. Six months after achieving CR, the transcript levels in BM decreased. Relapse was accompanied by secondary rise of the WT1-specific clone in PB but not in BM. In parallel, a lack of vaccine-induced WT1 specific IFNγ production was observed at that timepoint. In conclusion, we provide first data regarding evolution and compartmentalization of a peptide vaccine-induced T-cell clone in PB and BM of an AML patient. At the time of relapse, the same clone reappeared spontaneously in PB but not in BM showing impaired functionality.
authors.affiliation: Department of Hematology, Oncology, Charité Campus Benjamin Franklin, Berlin, Germany. sebastian.ochsenreither@charite.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ochsenreither
authors.forename: Alberto
authors.initials: A
authors.lastname: Fusi
authors.forename: Antonia
authors.initials: A
authors.lastname: Busse
authors.forename: Sandra
authors.initials: S
authors.lastname: Bauer
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: David
authors.initials: D
authors.lastname: Stather
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D009687:Nuclear Proteins / Q000276:immunology*; D016133:Polymerase Chain Reaction; D000072260:RNA Splicing Factors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D022223:Vaccines, Subunit; C419554:WTAP protein, human; D007371:Interferon-gamma