Improved Effector Function of Leukemia-specific T-lymphocyte Clones Trained with AML-derived Dendritic Cells

Cancer Genomics - Proteomics

ANJA LIEPERT⁴  CHRISTINE GRABRUCKER⁴  PETER LICHTNER³  RAYMUND BUHMANN¹  SUSANNE REUTHER²  FRIEDHELM R. SCHUSTER²  BERND HUBNER²  HELGA SCHMETZER¹  ARNDT BORKHARDT²  TING YANG³  HANS-JOCHEM KOLB⁴  TANJA KROELL⁴  ROLAND REIBKE⁴ 

[1] elmholtzZentrum München, German Research Center for Environmental Healthepartment for Hematopoietic Transplantation, University of Munich, GermanyelmholtzZentrum München, German Research Center for Environmental HealthelmholtzZentrum München, German Research Center for Environmental Healthepartment for Hematopoietic Transplantation, University of Munich, Germanyepartment for Hematopoietic Transplantation, University of Munich, GermanyelmholtzZentrum München, German Research Center for Environmental Healthepartment for Hematopoietic Transplantation, University of Munich, Germany;epartment of Pediatric Oncology, Hematology and Immunology, Heinrich Heine University Medical Center, Dusseldorfepartment of Pediatric Oncology, Hematology and Immunology, Heinrich Heine University Medical Center, Dusseldorfepartment of Pediatric Oncology, Hematology and Immunology, Heinrich Heine University Medical Center, Dusseldorf;elmholtzZentrum München, German Research Center for Environmental HealthelmholtzZentrum München, German Research Center for Environmental HealthelmholtzZentrum München, German Research Center for Environmental Health;epartment for Hematopoietic Transplantation, University of Munich, Germanyepartment for Hematopoietic Transplantation, University of Munich, Germanyepartment for Hematopoietic Transplantation, University of Munich, Germany

关键词: DC;    AML;    T-cells;    spectratyping;    immunotherapy;    stem cell transplantation;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

Recently it was shown that myeloid leukemic cells can be induced to differentiate into leukemia-derived dendritic cells (DCleu), regaining the stimulatory capacity of professional DCs while presenting the leukemic antigen repertoire. But so far, the induced antileukemic T-cell responses have varied in specificity and efficacy, or have even mediated opposite effects. In an attempt to further characterize the DC/DCleu induced T-cell response pattern, immunoscope spectratyping, a novel and powerful tool to detect T-cell receptor (TCR) rearrangements was used in combination with functional flow cytometry and non-radioactive fluorolysis assays. Human leucocyte antigen (HLA) matched donor T-cells were repeatedly stimulated, either with leukemic blasts (French-American-British, FAB M4eo) or the corresponding blast-derived DCs. Functional comparison revealed no significant difference in their T-cell stimulatory capacity, while the DC/DCleu fraction favored T-cells with a higher lytic activity, comprising a higher proportion of T-memory CD45R0+ cells. Stimulation with blasts and DC/DCleu induced a similar TCR restriction pattern, while stimulation with DC/DCleu favored the CD4 T-cell subset and seemed to cause a higher grade of restriction. In conclusion, a combined strategy using spectratyping with functional tests might not only provide useful information about the specificity and efficacy of the induced T-cell response, but also pave the way to gain effective T-cell clones for therapeutic use.

【 授权许可】

Unknown