Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia.

ABSTRACT: CRLF2 rearrangements occur in >50% of Ph-like and Down syndrome (DS)-associated B-acute lymphoblastic leukemia (ALL) and induce constitutive kinase signaling targetable by the JAK1/2 inhibitor ruxolitinib under current clinical investigation. While chimeric antigen receptor T cell (CART) immunotherapies have achieved remarkable remission rates in children with relapsed/refractory B-ALL, ~50% of CD19CART-treated patients relapse again, many with CD19 antigen loss. We previously reported preclinical activity of thymic stromal lymphopoietin receptor-targeted cellular immunotherapy (TSLPRCART) against CRLF2-overexpressing ALL as an alternative approach. In this study, we posited that combinatorial TSLPRCART and ruxolitinib would have superior activity and first validated potent TSLPRCART-induc

SUBMITTER: Balestra T 

PROVIDER: S-EPMC11879877 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature