scholarly journals Coexpressed Catalase Protects Chimeric Antigen Receptor–Redirected T Cells as well as Bystander Cells from Oxidative Stress–Induced Loss of Antitumor Activity

2015 ◽  
Vol 196 (2) ◽  
pp. 759-766 ◽  
Author(s):  
Maarten A. Ligtenberg ◽  
Dimitrios Mougiakakos ◽  
Madhura Mukhopadhyay ◽  
Kristina Witt ◽  
Alvaro Lladser ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Antitumor Activity ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Bystander Cells

scholarly journals Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo

2013 ◽  
Vol 1 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Evripidis Lanitis ◽  
Mathilde Poussin ◽  
Alex W. Klattenhoff ◽  
Degang Song ◽  
Raphael Sandaltzopoulos ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Activity ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Signaling Domains

scholarly journals Mesothelin-Specific Chimeric Antigen Receptor mRNA-Engineered T Cells Induce Antitumor Activity in Solid Malignancies

2013 ◽  
Vol 2 (2) ◽  
pp. 112-120 ◽  
Author(s):  
Gregory L. Beatty ◽  
Andrew R. Haas ◽  
Marcela V. Maus ◽  
Drew A. Torigian ◽  
Michael C. Soulen ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Activity ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Receptor Mrna ◽  
Solid Malignancies ◽  
Engineered T Cells

Blocking CD38-driven fratricide among T cells enables effective antitumor activity by CD38-specific chimeric antigen receptor T cells

2019 ◽  
Vol 46 (8) ◽  
pp. 367-377 ◽  
Author(s):  
Zhitao Gao ◽  
Chuan Tong ◽  
Yao Wang ◽  
Deyun Chen ◽  
Zhiqiang Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Activity ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor

Safety and antitumor activity of chimeric antigen receptor modified T cells in patients with chemotherapy refractory metastatic pancreatic cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3007-3007 ◽  
Author(s):  
Gregory Lawrence Beatty ◽  
Mark H. O'Hara ◽  
Anne M Nelson ◽  
Maureen McGarvey ◽  
Drew A. Torigian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Antitumor Activity ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Metastatic Pancreatic Cancer

Abstract B129: Chimeric antigen receptor T-cells targeting the αvβ6 integrin demonstrate potent antitumor activity in multiple solid tumors

2016 ◽  
Author(s):  
Lynsey May Whilding ◽  
Ana C. Parente-Pereira ◽  
Tomasz Zabinski ◽  
David M. Davies ◽  
Roseanna Petrovic ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Αvβ6 Integrin

A chimeric antigen receptor with antigen-independent OX40 signaling mediates potent antitumor activity

2021 ◽  
Vol 13 (578) ◽  
pp. eaba7308
Author(s):  
Huihui Zhang ◽  
Fanlin Li ◽  
Jiang Cao ◽  
Xin Wang ◽  
Hai Cheng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Mouse Tumor ◽  
Great Success ◽  
Car T Cells ◽  
Car T

Although chimeric antigen receptor (CAR)–modified T cells have shown great success in the treatment of B cell malignancies, this approach has limited efficacy in patients with solid tumors. Various modifications in CAR structure have been explored to improve this efficacy, including the incorporation of two costimulatory domains. Because costimulatory signals are transduced together with T cell receptor signals during T cell activation, we engineered a type of CAR-T cells with a costimulatory signal that was activated independently from the tumor antigen to recapitulate physiological stimulation. We screened 12 costimulatory receptors to identify OX40 as the most effective CAR-T function enhancer. Our data indicated that these new CAR-T cells showed superior proliferation capability compared to current second-generation CAR-T cells. OX40 signaling reduced CAR-T cell apoptosis through up-regulation of genes encoding Bcl-2 family members and enhanced proliferation through increased activation of the NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase), and PI3K-AKT (phosphoinositide 3-kinase to the kinase AKT) pathways. OX40 signaling not only enhanced the cytotoxicity of CAR-T cells but also reduced exhaustion markers, thereby maintaining their function in immunosuppressive tumor microenvironments. In mouse tumor models and in patients with metastatic lymphoma, these CAR-T cells exhibited robust amplification and antitumor activity. Our findings provide an alternative option for CAR-T optimization with the potential to overcome the challenge of treating solid tumors.

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