Pre-TCR-targeted immunotherapy for T cell acute lymphoblastic leukemia.

ABSTRACT: Targeted immunotherapy for T cell acute lymphoblastic leukemia (T-ALL), an aggressive tumor of developing T cell progenitors, is an urgent unmet need, especially for relapsed/refractory disease. Selective T-ALL targeting is challenging due to the shared antigen expression between leukemic and normal T cells. Here we identify the pre-T cell receptor (pre-TCR), a surface receptor essential for T cell development, as a biomarker of leukemia-initiating cells (LICs) in human T-ALL. Loss-of-function genetic approaches demonstrate that pre-TCR signaling is necessary for LIC activity and tumor progression in pre-TCR⁺ T-ALL patient xenografts in mice. Furthermore, we demonstrate the specific therapeutic targeting of the pre-TCR with a monoclonal antibody against the invariant pTα subunit

SUBMITTER: Fuentes P 

PROVIDER: S-EPMC12479361 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature