CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges

被引:264
作者
Bagley, Stephen J. [1 ]
Desai, Arati S. [1 ]
Linette, Gerald P. [1 ,2 ]
June, Carl H. [1 ,2 ]
O'Rourke, Donald M. [1 ,3 ]
机构
[1] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Ctr Cellular Immunotherapies, Philadelphia, PA 19104 USA
[3] Univ Penn, Perelman Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA
关键词
CAR; EGFRvIII; glioblastoma; immunotherapy; T cells; CENTRAL-NERVOUS-SYSTEM; CHIMERIC ANTIGEN RECEPTORS; BLOOD-BRAIN-BARRIER; STEM-CELLS; TUMOR-IMMUNOTHERAPY; IMMUNE RESISTANCE; PD-1; BLOCKADE; VARIANT-III; GLIOMA; EXPRESSION;
D O I
10.1093/neuonc/noy032
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T-cell therapy for glioblastoma. In addition, despite formidable barriers to T-cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients. In this review, we begin with a discussion of established obstacles to systemic therapy in glioblastoma and how these may be overcome by CAR T cells. We continue with a summary of previously published CAR T-cell trials in GBM, and end by outlining the key therapeutic challenges associated with the use of CAR T cells in this disease.
引用
收藏
页码:1429 / 1438
页数:10
相关论文
共 92 条
[1]
Driving CARs on the Highway to Solid Cancer: Some Considerations on the Adoptive Therapy with CAR T Cells [J].
Abken, Hinrich .
HUMAN GENE THERAPY, 2017, 28 (11) :1047-1060
[2]
HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma A Phase 1 Dose-Escalation Trial [J].
Ahmed, Nabil ;
Brawley, Vita ;
Hegde, Meenakshi ;
Bielamowicz, Kevin ;
Kalra, Mamta ;
Landi, Daniel ;
Robertson, Catherine ;
Gray, Tara L. ;
Diouf, Oumar ;
Wakefield, Amanda ;
Ghazi, Alexia ;
Gerken, Claudia ;
Yi, Zhongzhen ;
Ashoori, Aidin ;
Wu, Meng-Fen ;
Liu, Hao ;
Rooney, Cliona ;
Dotti, Gianpietro ;
Gee, Adrian ;
Su, Jack ;
Kew, Yvonne ;
Baskin, David ;
Zhang, Yi Jonathan ;
New, Pamela ;
Grilley, Bambi ;
Stojakovic, Milica ;
Hicks, John ;
Powell, Suzanne Z. ;
Brenner, Malcolm K. ;
Heslop, Helen E. ;
Grossman, Robert ;
Wels, Winfried S. ;
Gottschalk, Stephen .
JAMA ONCOLOGY, 2017, 3 (08) :1094-1101
[3]
HER2-Specific T Cells Target Primary Glioblastoma Stem Cells and Induce Regression of Autologous Experimental Tumors [J].
Ahmed, Nabil ;
Salsman, Vita S. ;
Kew, Yvonne ;
Shaffer, Donald ;
Powell, Suzanne ;
Zhang, Yi J. ;
Grossman, Robert G. ;
Heslop, Helen E. ;
Gottschalk, Stephen .
CLINICAL CANCER RESEARCH, 2010, 16 (02) :474-485
[4]
Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas [J].
Andersson, U ;
Guo, D ;
Malmer, B ;
Bergenheim, AT ;
Brännström, T ;
Hedman, H ;
Henriksson, R .
ACTA NEUROPATHOLOGICA, 2004, 108 (02) :135-142
[5]
Immunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma [J].
Antonios, Joseph P. ;
Soto, Horacio ;
Everson, Richard G. ;
Moughon, Diana ;
Orpilla, Joey R. ;
Shin, Namjo P. ;
Sedighim, Shaina ;
Treger, Janet ;
Odesa, Sylvia ;
Tucker, Alexander ;
Yong, William H. ;
Li, Gang ;
Cloughesy, Timothy F. ;
Liau, Linda M. ;
Prins, Robert M. .
NEURO-ONCOLOGY, 2017, 19 (06) :796-807
[6]
Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma [J].
Bielamowicz, Kevin ;
Fousek, Kristen ;
Byrd, Tiara T. ;
Samaha, Hebatalla ;
Mukherjee, Malini ;
Aware, Nikita ;
Wu, Meng-Fen ;
Orange, Jordan S. ;
Sumazin, Pavel ;
Man, Tsz-Kwong ;
Joseph, Sujith K. ;
Hegde, Meenakshi ;
Ahmed, Nabil .
NEURO-ONCOLOGY, 2018, 20 (04) :506-518
[7]
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy [J].
Brown, Christine E. ;
Alizadeh, Darya ;
Starr, Renate ;
Weng, Lihong ;
Wagner, Jamie R. ;
Naranjo, Araceli ;
Ostberg, Julie R. ;
Blanchard, M. Suzette ;
Kilpatrick, Julie ;
Simpson, Jennifer ;
Kurien, Anita ;
Priceman, Saul J. ;
Wang, Xiuli ;
Harshbarger, Todd L. ;
D'Apuzzo, Massimo ;
Ressler, Julie A. ;
Jensen, Michael C. ;
Barish, Michael E. ;
Chen, Mike ;
Portnow, Jana ;
Forman, Stephen J. ;
Badie, Behnam .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (26) :2561-2569
[8]
Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma [J].
Brown, Christine E. ;
Badie, Behnam ;
Barish, Michael E. ;
Weng, Lihong ;
Ostberg, Julie R. ;
Chang, Wen-Chung ;
Naranjo, Araceli ;
Starr, Renate ;
Wagner, Jamie ;
Wright, Christine ;
Zhai, Yubo ;
Bading, James R. ;
Ressler, Julie A. ;
Portnow, Jana ;
D'Apuzzo, Massimo ;
Forman, Stephen J. ;
Jensen, Michael C. .
CLINICAL CANCER RESEARCH, 2015, 21 (18) :4062-4072
[9]
Glioma IL13Rα2 Is Associated with Mesenchymal Signature Gene Expression and Poor Patient Prognosis [J].
Brown, Christine E. ;
Warden, Charles D. ;
Starr, Renate ;
Deng, Xutao ;
Badie, Behnam ;
Yuan, Yate-Ching ;
Forman, Stephen J. ;
Barish, Michael E. .
PLOS ONE, 2013, 8 (10)
[10]
Stem-like Tumor-Initiating Cells Isolated from IL13Rα2 Expressing Gliomas Are Targeted and Killed by IL13-Zetakine-Redirected T Cells [J].
Brown, Christine E. ;
Starr, Renate ;
Aguilar, Brenda ;
Shami, Andrew F. ;
Martinez, Catalina ;
D'Apuzzo, Massimo ;
Barish, Michael E. ;
Forman, Stephen J. ;
Jensen, Michael C. .
CLINICAL CANCER RESEARCH, 2012, 18 (08) :2199-2209