Targeting hypoxia downstream signaling protein, CAIX, for CAR T-cell therapy against glioblastoma.

ABSTRACT:

Background

Glioblastoma survival remains unchanged despite continuing therapeutic innovation. Herein, we aim to (i) develop chimeric antigen receptor (CAR) T cells with a specificity to a unique antigen, carbonic anhydrase IX (CAIX), which is expressed in the hypoxic microenvironment characteristic of glioblastoma, and (ii) demonstrate its efficacy with limited off-target effects.

Methods

First we demonstrated expression of CAIX in patient-derived glioblastoma samples and available databases. CAR T cells were generated against CAIX and efficacy was assessed in 4 glioblastoma cell lines and 2 glioblastoma stem cell lines. Cytotoxicity of anti-CAIX CAR T cells was assessed via interferon gamma, tumor necrosis factor alpha, and interleukin-2 levels when co-cultured with tumor c

SUBMITTER: Cui J 

PROVIDER: S-EPMC6827823 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature