Immunmodulatorische Wirkung von Lenalidomid auf die peptidspezifische Immunantwort durch CD8+ T-Lymphozyten

Abstract

In the treatment of patients with hematologic malignancies, targeted immunotherapies become more important. One promising option is the vaccination with leukemia-associated antigens. Several leukemia-associated antigens have been identified and some of them like RHAMM, Proteinase-3 and WT-1 have been already tested in clinical peptide vaccination trials with immunological and clinical responses. The aim of this study was to investigate whether the specific T cell response against the leukemia-associated antigens RHAMM-R3, PRAME-P3 and Aurorakinase-A2 is enhanced by the immunomodulatory drug lenalidomide in vitro. Blood samples from 10 healthy volunteers were tested with regard to an induction of a specific CD8+ T-cells response against the leukemia-associated antigens. For the samples we used Lenalidomid in a dose of 5µM. Ag-specific activation was analyzed by IFN-Gamma and Granzyme B secretion using ELISPOT assay. In the majority of samples tested, we found that activation of peptid-specific T-cells from healthy donors was enhanced by lenalidomide and furthermore that the impact of lenalidomide on T-cells depends on the dose. Taken together, Lenalidomid has a costimulatory, dose-dependent impact on Ag-specific CD8+ T-cells.