scholarly journals Tumor-Specific Reactive Oxygen Species Accelerators Improve Chimeric Antigen Receptor T Cell Therapy in B Cell Malignancies

2019 ◽  
Vol 20 (10) ◽  
pp. 2469 ◽  
Author(s):  
Hyeon Joo Yoo ◽  
Yibin Liu ◽  
Lei Wang ◽  
Maria-Luisa Schubert ◽  
Jean-Marc Hoffmann ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Reactive Oxygen ◽  
Treatment Resistance ◽  
Lymphocytic Leukemia ◽  
Oxygen Species ◽  
T Cell Therapy

Chimeric antigen receptor T cell (CART) therapy is currently one of the most promising treatment approaches in cancer immunotherapy. However, the immunosuppressive nature of the tumor microenvironment, in particular increased reactive oxygen species (ROS) levels, provides considerable limitations. In this study, we aimed to exploit increased ROS levels in the tumor microenvironment with prodrugs of ROS accelerators, which are specifically activated in cancer cells. Upon activation, ROS accelerators induce further generation of ROS. This leads to an accumulation of ROS in tumor cells. We hypothesized that the latter cells will be more susceptible to CARTs. CD19-specific CARTs were generated with a CD19.CAR.CD28.CD137zeta third-generation retroviral vector. Cytotoxicity was determined by chromium-51 release assay. Influence of the ROS accelerators on viability and phenotype of CARTs was determined by flow cytometry. The combination of CARTs with the ROS accelerator PipFcB significantly increased their cytotoxicity in the Burkitt lymphoma cell lines Raji and Daudi, as well as primary chronic lymphocytic leukemia cells. Exposure of CARTs to PipFcB for 48 h did not influence T cell exhaustion, viability, or T cell subpopulations. In summary, the combination of CARTs with ROS accelerators may improve adoptive immunotherapy and help to overcome tumor microenvironment-mediated treatment resistance.

scholarly journals Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xinfeng Chen ◽  
Mengjia Song ◽  
Bin Zhang ◽  
Yi Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Reactive Oxygen ◽  
Cell Immune Response ◽  
Oxygen Species ◽  
Cell Based Therapy ◽  
Immunosuppressive Cells

Reactive oxygen species (ROS) produced by cellular metabolism play an important role as signaling messengers in immune system. ROS elevated in the tumor microenvironment are associated with tumor-induced immunosuppression. T cell-based therapy has been recently approved to be effective for cancer treatment. However, T cells often become dysfunctional after reaching the tumor site. It has been reported that ROS participate extensively in T cells activation, apoptosis, and hyporesponsiveness. The sensitivity of T cells to ROS varies among different subsets. ROS can be regulated by cytokines, amino acid metabolism, and enzymatic activity. Immunosuppressive cells accumulate in the tumor microenvironment and induce apoptosis and functional suppression of T cells by producing ROS. Thus, modulating the level of ROS may be important to prolong survival of T cells and enhance their antitumor function. Combining T cell-based therapy with antioxidant treatment such as administration of ROS scavenger should be considered as a promising strategy in cancer treatment, aiming to improve antitumor T cells immunity.

Chimeric Antigen Receptor T-Cell Therapy for Chronic Lymphocytic Leukemia: A Narrative Review

2017 ◽  
Vol 17 (12) ◽  
pp. 852-856 ◽  
Author(s):  
Anthony R. Mato ◽  
Meghan C. Thompson ◽  
Chadi Nabhan ◽  
Jakub Svoboda ◽  
Stephen J. Schuster
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Narrative Review ◽  
Lymphocytic Leukemia ◽  
T Cell Therapy

scholarly journals Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia

2018 ◽  
Vol 24 (5) ◽  
pp. 563-571 ◽  
Author(s):  
Joseph A. Fraietta ◽  
Simon F. Lacey ◽  
Elena J. Orlando ◽  
Iulian Pruteanu-Malinici ◽  
Mercy Gohil ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Lymphocytic Leukemia ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Author Correction: Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia

2021 ◽  
Vol 27 (3) ◽  
pp. 561-561
Author(s):  
Joseph A. Fraietta ◽  
Simon F. Lacey ◽  
Elena J. Orlando ◽  
Iulian Pruteanu-Malinici ◽  
Mercy Gohil ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Lymphocytic Leukemia ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigen receptor T cells immunotherapy: challenges and opportunities in hematological malignancies

Immunotherapy ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 1341-1357
Author(s):  
Nashwa El-Khazragy ◽  
Sherief Ghozy ◽  
Passant Emad ◽  
Mariam Mourad ◽  
Diaaeldeen Razza ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Hematological Malignancies ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Challenges And Opportunities

Taking advantage of the cellular immune system is the mainstay of the adoptive cell therapy, to induce recognition and destruction of cancer cells. The impressive demonstration of this principle is chimeric antigen receptor-modified T (CAR-T)-cell therapy, which had a major impact on treating relapsed and refractory hematological malignancies. Despite the great results of the CAR-T-cell therapy, many tumors are still able to avoid immune detection and further elimination, as well as the possible associated adverse events. Herein, we highlighted the recent advances in CAR-T-cell therapy, discussing their applications beneficial functions and side effects in hematological malignancies, illustrating the underlying challenges and opportunities. Furthermore, we provide an overview to overcome different obstacles using potential manufacture and treatment strategies.

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