Targeting the residual malignant clone in myeloid leukemia using NK cell-stimulatory immunotherapy

During the last years, we have characterized the immunobiology of patients receiving IL-2-based immunotherapy in acute myeloid leukemia (AML).

With this research proposal, we aim to further delineate how different genetic variants impact on NK cell effector functions and clinical outcome of patients with myeloid malignancies.

This research program also comprises experimental and clinical studies on the role of NK cells for the eradication of myeloid leukemic cells. The proposed studies will address the purported role of NK cells for treatment-free remission in CML.

The clinical trial may provide the first proof-of-principle that the addition of an NK-stimulatory regimen to TKI therapy can enhance the anti-leukemic response and possibly contribute to the eradication of the residual leukemia.In the project, we will develop a method, which makes it possible to combine high-throughput transcriptomic and protein profiling with bcr/abl1 genomic information in single leukemic blasts.

This characterization of leukemic stem cells may lead to identification of novel biomarkers that may be useful to prognosticate patients.

In a related ligand identification project, we will use pre-engineered cell lines to skew interactions towards the receptor in question.

This is a novel strategy that has great potential to identify new structures, and the identification of the NKp46L would be a major discovery with broad impact on our understanding of NK cell recognition of malignant cells.