Armoring STEAP1 CAR T cells with IL-18 potentiates antitumor activity in Ewing sarcoma.

ABSTRACT:

Background

Ewing sarcoma (EwS) is a highly aggressive cancer driven by the EWS::FLI1 fusion oncoprotein affecting children, adolescents, and young adults. Six transmembrane epithelial antigen 1 (STEAP1) is a cell surface antigen transcriptionally controlled by EWS::FLI1 that is broadly expressed in EwS, positioning it as a rational immunotherapy target. However, translating CAR T therapy to solid tumors requires overcoming barriers to potency while maintaining safety.

Methods

Analyses of transcriptome and proteome data were performed to evaluate the effects of EWS::FLI1 perturbation on STEAP1 expression at the transcript and protein levels in EwS models. STEAP1 expression was validated in EwS patient tissues by immunohistochemistry. Second-generation STEAP1-BBζ CAR T cells w

SUBMITTER: Bhatia V 

PROVIDER: S-EPMC12710653 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature