Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight

Journal of Translational Medicine

Craig A. Land¹  Phillip R. Musich¹  Qian Xie²  Dalia Haydar³  Giedre Krenciute³ 

[1] Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, 37614, Johnson City, TN, USA;Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, 37614, Johnson City, TN, USA;Center of Excellence for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, 37614, Johnson City, TN, USA;Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, 38105, Memphis, TN, USA;

关键词: Chimeric antigen receptors;    CAR;    T-cell therapy;    Glioblastoma;    Cellular immunotherapy;   

DOI  :  10.1186/s12967-020-02598-0

来源: Springer

【 摘 要 】

Glioblastoma multiforme (GBM) is the most common malignant brain cancer that invades normal brain tissue and impedes surgical eradication, resulting in early local recurrence and high mortality. In addition, most therapeutic agents lack permeability across the blood brain barrier (BBB), further reducing the efficacy of chemotherapy. Thus, effective treatment against GBM requires tumor specific targets and efficient intracranial drug delivery. With the most recent advances in immunotherapy, genetically engineered T cells with chimeric antigen receptors (CARs) are becoming a promising approach for treating cancer. By transducing T lymphocytes with CAR constructs containing a tumor-associated antigen (TAA) recognition domain linked to the constant regions of a signaling T cell receptor, CAR T cells may recognize a predefined TAA with high specificity in a non-MHC restricted manner, and is independent of antigen processing. Active T cells can travel across the BBB, providing additional advantage for drug delivery and tumor targeting. Here we review the CAR design and technical innovations, the major targets that are in pre-clinical and clinical development with a focus on GBM, and multiple strategies developed to improve CAR T cell efficacy.

【 授权许可】

CC BY