Mesenchymal Stromal Cells do not suppress CAR-T function in B-Cell Precursor Acute Lymphoblastic Leukemia

CD19-directed CAR T-cell therapy for pediatric relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) revealed promising short-term outcome results. However, still 50% of these cases relapse within 2 years after CAR T-cell infusion. Our previous research showed that BCP-ALL hijack the bone marrow niche resulting in increased leukemic cell survival, chemotherapy resistance and immunosuppression. Our aim is to investigate whether MSCs in the bone marrow niche impact the killing efficacy of CAR T-cells. Ex vivo CAR-T efficacy assays of 10 diagnostic BCP-ALL bone marrow aspirates were performed by coculturing BCP-ALL cells with MSCs for 40h, mimicking the ALL-educated niche ex vivo. This was followed by exposure to CAR T-cells for 24h and flow cytometry to assess survival of BCP-ALL cells. For 80% (8/10) of the samples, there was no difference or even more CAR T-mediated killing seen in coculture with MSCs compared to monoculture, showing that MSCs do not protect BCP-ALL cells against CAR T-mediated killing in this in vitro setting. Ongoing experiments will show whether CAR-T function is affected by coculture with other differentiated stromal layers.

Publication History

Article published online:
09 May 2025