scholarly journals Therapeutic potential of CAR T cell in malignancies: A scoping review

2022 ◽  
Vol 146 ◽  
pp. 112512
Author(s):  
Ali Zarezadeh Mehrabadi ◽  
Reza Ranjbar ◽  
Mahdieh Farzanehpour ◽  
Alireza Shahriary ◽  
Ruhollah Dorostkar ◽  
...  
Oncotarget ◽  
2015 ◽  
Vol 6 (42) ◽  
pp. 44179-44190 ◽  
Author(s):  
Xiang-Jun Tang ◽  
Xu-Yong Sun ◽  
Kuan-Ming Huang ◽  
Li Zhang ◽  
Zhuo-Shun Yang ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 139 ◽  
Author(s):  
Jing Cui ◽  
Herui Wang ◽  
Rogelio Medina ◽  
Qi Zhang ◽  
Chen Xu ◽  
...  

Chimeric antigen receptor (CAR)-engineered T cells represent a promising modality for treating glioblastoma. Recently, we demonstrated that CAR-T cells targeting carbonic anhydrase IX (CAIX), a protein involved in HIF-1a hypoxic signaling, is a promising CAR-T cell target in an intracranial murine glioblastoma model. Anti-CAIX CAR-T cell therapy is limited by its suboptimal activation within the tumor microenvironment. LB-100, a small molecular inhibitor of protein phosphatase 2A (PP2A), has been shown to enhance T cell anti-tumor activity through activation of the mTOR signaling pathway. Herein, we investigated if a treatment strategy consisting of a combination of LB-100 and anti-CAIX CAR-T cell therapy produced a synergistic anti-tumor effect. Our studies demonstrate that LB-100 enhanced anti-CAIX CAR-T cell treatment efficacy in vitro and in vivo. Our findings demonstrate the role of LB-100 in augmenting the cytotoxic activity of anti-CAIX CAR-T cells and underscore the synergistic therapeutic potential of applying combination LB-100 and CAR-T Cell therapy to other solid tumors.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Liat Rousso-Noori ◽  
Ignacio Mastandrea ◽  
Shauli Talmor ◽  
Tova Waks ◽  
Anat Globerson Levin ◽  
...  

AbstractGlioblastoma is considered one of the most aggressive malignancies in adult and pediatric patients. Despite decades of research no curative treatment is available and it thus remains associated with a very dismal prognosis. Although recent pre-clinical and clinical studies have demonstrated the feasibility of chimeric antigen receptors (CAR) T cell immunotherapeutic approach in glioblastoma, tumor heterogeneity and antigen loss remain among one of the most important challenges to be addressed. In this study, we identify p32/gC1qR/HABP/C1qBP to be specifically expressed on the surface of glioma cells, making it a suitable tumor associated antigen for redirected CAR T cell therapy. We generate p32 CAR T cells and find them to recognize and specifically eliminate p32 expressing glioma cells and tumor derived endothelial cells in vitro and to control tumor growth in orthotopic syngeneic and xenograft mouse models. Thus, p32 CAR T cells may serve as a therapeutic option for glioblastoma patients.


2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v108-v120
Author(s):  
Leeann B Burton ◽  
Mahsa Eskian ◽  
Amanda C Guidon ◽  
Kerry L Reynolds

Abstract Immuno-oncology agents, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T (CAR-T) cell therapies, are increasing in use for a growing list of oncologic indications. While harnessing the immune system against cancer cells has a potent anti-tumor effect, it can also cause widespread autoimmune toxicities that limit therapeutic potential. Neurologic toxicities have unique presentations and can progress rapidly, necessitating prompt recognition. In this article, we review the spectrum of central and peripheral neurologic immune-related adverse events (irAEs) associated with ICI therapies, emphasizing a diagnostic framework that includes consideration of the therapy regimen, timing of symptom onset, presence of non-neurologic irAEs, pre-existing neurologic disease, and syndrome specific features. In addition, we review the immune effector cell-associated neurotoxicity syndrome (ICANS) associated with CAR-T cell therapy and address diagnostic challenges specific to patients with brain metastases. As immunotherapy use grows, so too will the number of patients affected by neurotoxicity. There is an urgent need to understand pathogenic mechanisms, predictors, and optimal treatments of these toxicities, so that we can manage them without sacrificing anti-tumor efficacy.


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