Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape.

ABSTRACT: CD19 chimeric antigen receptors (CARs) have demonstrated great efficacy against a range of B cell malignancies. However, antigen escape and, more generally, heterogeneous antigen expression pose a challenge to applying CAR therapy to a wide range of cancers. We find that low-dose radiation sensitizes tumor cells to immune rejection by locally activated CAR T cells. In a model of pancreatic adenocarcinoma heterogeneously expressing sialyl Lewis-A (sLeA), we show that not only sLeA⁺ but also sLeA^- tumor cells exposed to low-dose radiation become susceptible to CAR therapy, reducing antigen-negative tumor relapse. RNA sequencing analysis of low-dose radiation-exposed tumors reveals the transcriptional signature of cells highly sensitive to TRAIL-mediated death. We find t

SUBMITTER: DeSelm C 

PROVIDER: S-EPMC6225039 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature