PD1CD28 Chimeric Molecule Enhances EGFRvⅢ Specific CAR-T Cells in Xenograft Experiments in Mouse Models

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Oct 1

PMID 39352918

Authors

Wanqiong Chen

Na Xian

Ningning Zhao

Qiong Zhang

Yunlu Xu

Affiliations

Soon will be listed here.

Abstract

Over the years, CAR-T cell therapy has achieved remarkable success in treating hematological malignancies. However, this efficacy has not been replicated in the context of glioblastoma (GBM). In this study, a PD1CD28 chimeric molecule was introduced into EGFRvⅢ-directed CAR-T cells, generating EGFRvⅢ-P2A-PD1CD28 CAR-T cells. Notably, this modification significantly increased IL-2 secretion and enhanced antigen-dependent activation of CAR-T cells, especially when programmed cell death ligand 1 (PD-L1) was present in vitro. In addition, the in vivo xenograft experiments revealed that the PD1CD28 chimeric molecule played a pivotal role in reducing recurrence rates, effectively controlling recurrent tumor volume, and ultimately prolonging the survival of mice. Collectively, these findings suggest that EGFRvⅢ-directed CAR-T cells co-expressing the PD1CD28 chimeric molecule have the potential to significantly enhance the treatment efficacy against GBM.

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