Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma.

ABSTRACT:

Introduction

Chimeric antigen receptor (CAR) T-cell therapy is a promising and innovative cancer therapy. However, immunosuppressive tumor microenvironments (TME) limit T cell persistence and durable efficacy. Here, we aimed to identify and target immunosuppressive factors in the TME of neuroblastoma, a pediatric extracranial solid tumor, to improve CAR-T efficacy.

Methods

Immunosuppressive factors were identified using a multi-omics approach, including single-cell RNA sequencing (scRNA-seq) of 24 neuroblastoma tumors, published bulk-RNA sequencing datasets, and mass-spectrometry of patient-derived tumoroid models. Candidate targets were validated with functional assays in vitro and in vivo. Protein degradation of the top immunosuppressive target by PROTAC technology was use

SUBMITTER: Strijker JGM 

PROVIDER: S-EPMC11884407 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature