Year: 2016
Type: article
Abstract: Gliomas are the most common primary malignant brain tumor and are uniformly lethal. Cancer immunotherapy has the potential to target gliomas; however, its antitumor effects are restricted by limitations in clinically useful tumor specific targets. Chimeric antigen receptor modified T-cell (CAR-T) therapy is a highly promising option for cancer treatment, due to its combination of precision antibody recognition and T-cell tumor-specific killing. CD70 is an antigen expressed by limited subsets of normal lymphocytes and dendritic cells but is aberrantly overexpressed by glioma cells, which makes it an outstanding glioma-antigen target. The gene and protein expression of CD70 were evaluated to identify its potential as a glioma target. Human and mouse versions of CD70-specific CAR-T cells were generated, and human primary GBM lines as well as murine lines (GL-261, KR-158B) were used as human and mouse tumor targets, respectively. The antitumor effect of the human and mouse CD70-sepecific CARs were tested in vitro and in an orthotopic murine syngeneic model in vivo. CD70 is only overexpressed by tumor cells in a subset of low-grade gliomas and GBM. The elevated gene and protein expression are associated with increased tumor grade and poor patient survival. Co-culturing CD70-specific CAR-T cells with CD70-positive glioma cells resulted in potent secretion of IFN-gamma and tumor-specific killing in a CD70-dependent manner. Irradiation enhances CD70 expression on glioma cells and thus increases CAR T-cell recognition. Adoptive transferring of the CD70 CAR-T cells resulted in total regression of gliomas in the brain of immunocompetent mice. CD70 can be an excellent tumor target for gliomas, and CD70-specific CAR-T cells have potent antitumor activity against CD70-positive gliomas both in vitro and in vivo. Our study provides crucial preclinical evidence to support the future clinical application of CD70 CAR-T cells to treat gliomas.
Source: Neuro-Oncology
Authors: Linchun Jin, Haitao Ge, Changlin Yang, Yu Long, Yifan Chang, Luyan Mu, Elias Sayour, Gabriel De Leon, Qiong Wang, James Yang, Jeffrey Drake, Paul Kubilis, Hongbo Bao, Songsong Xia, Dunyue Lu, Yingjun Kong, Li Hu, Yibo Yin, Yujiao Shang, Chencheng Jiang, Jing Nie, Shimin Li, Jiping Qi, Yunhe Gu, Jiahang Sun, Zhiguo Lin, Duane Mitchell, Jianping Huang
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2589069470