Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models.

ABSTRACT:

Purpose

Clinical efficacy of chimeric antigen receptor (CAR) T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We sought to determine the primary chemokines secreted by OS and evaluate the efficacy of B7-H3.CAR T cells expressing the cognate receptors.

Experimental design

We developed a pipeline to identify chemokines secreted by OS by correlating RNA-seq data with chemokine protein detected in media from fresh surgical specimens. We identified CXCR2 and CXCR6 as promising receptors for enhancing CAR T-cell homing against OS. We evaluated the homing kinetics and efficiency of CXCR2- and CXCR6.T cells and homing, cytokine production, and antitumor activity of CXCR2

SUBMITTER: Talbot LJ 

PROVIDER: S-EPMC11443211 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature