Clinical Research Directory

Study of an Innovative Therapy Using CAR-T Cells Targeting IL-1RAP in Patients With High-Risk Myelodysplastic Syndromes (MDS

Sponsor: University Hospital, Grenoble

Summary

The surface protein IL-1RAP, expressed by leukemic blast cells, represents a target of interest for patients with acute myeloid leukemia (AML). Its restricted and specific expression on leukemic cells makes it a promising target for chimeric antigen receptor T-cell (CAR-T cell) immunotherapy. High-risk myelodysplastic syndromes (MDS) correspond to a pre-leukemic condition characterized by an accumulation of bone marrow blasts. Unfortunately, very few effective treatments are currently available, apart from allogeneic hematopoietic stem cell transplantation, which can only be performed in a limited number of patients. It has been demonstrated that high-risk MDS blasts express IL-1RAP. The project will aim to: * Confirm IL-1RAP expression on primary MDS blast cells. * Measure circulating soluble IL-1RAP in plasma samples from MDS patients. * Investigate the interaction with the microenvironment in relation to IL-1RAP cellular expression. * Evaluate the effect of first-line standard treatment for MDS on IL-1RAP surface expression. * Assess the in vitro efficacy of an IL-1RAP-targeted CAR-T cell on MDS leukemic stem cells. * Assess the in vivo efficacy of an IL-1RAP-targeted CAR-T cell in a humanized murine model of MDS. To successfully conduct this project, it is essential to collect blood and bone marrow samples from high-risk MDS patients This project will require the collection of bone marrow and blood samples from patients with MDS, either newly diagnosed or currently undergoing treatment.

Official title: Role of IL-1RAP in the Pathophysiology of Myelodysplastic Syndromes and Its Use as a Target for Immunotherapy

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