CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Patient with Myelodysplastic Syndrome (MDS)
* Low-risk MDS according to the IPSS-M (20).
* MDS confirmed by bone marrow cytology with a blast percentage between 5% and 19% and/or associated with cytogenetic abnormalities or gene mutations indicating poor prognosis.
* High-risk MDS according to the IPSS-M
* At diagnosis or in cases of relapse/refractoriness to hypomethylating agents or to allogeneic hematopoietic stem cell transplantation.

Exclusion Criteria:

* Patient not diagnosed with MDS or patient diagnosed with acute myeloid leukemia.
* Patient with an active solid tumor or another active hematologic malignancy requiring treatment.
* Patient with a contraindication to performing bone marrow aspiration.
* Individuals referred to in Articles L1121-6 to L1121-8 of the French Public Health Code

主要终点：Validation of IL-1RAP CAR-T Cell Efficacy: · In vitro: Co-culture of CD34⁺ hematopoietic stem cells from high-risk MDS patients with IL-1RAP CAR-T cells: 1) to assess cytotoxicity (% of cell death), 2) including measurement of IFN-γ, TNF, granzyme, and perforin secretion. In vivo: Evaluation of the therapeutic effect of IL-1RAP CAR-T cells in a murine xenograft model using CD34⁺ MDS HSCs previously engineered to express the luciferase gene, with therapeutic efficacy assessed by reduction in bioluminescence (%). · Baseline through study completion, an average of 1 year

• MDS patients with low and high risk MDS · EXPERIMENTAL

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.