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Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

Frontiers of Medicine 2020, Volume 14, Issue 6,   Pages 726-745 doi: 10.1007/s11684-020-0746-0

Abstract: Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblasticHowever, CAR T cells have achieved minimal success against solid malignancies because of the additionalMobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeuticthe immune response in solid malignancies, especially with CAR T cells acting as cellular carriers toFinally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance

Keywords： CAR T cells     immunoregulatory molecules     endogenous immune response     solid malignancies    

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CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

Frontiers of Medicine 2021, Volume 15, Issue 6,   Pages 783-804 doi: 10.1007/s11684-021-0904-z

Abstract: Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematologicalIn this review, through a representative case study, we summarize the current experience of CAR T-celleffects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CART-cell therapy.

Keywords： CAR T cells     hematological malignancies     review    

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

Frontiers of Medicine 2022, Volume 16, Issue 3,   Pages 322-338 doi: 10.1007/s11684-021-0901-2

Abstract: To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatmentHowever, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or theyThe simultaneous expression of target antigens by healthy organs and tumor cells is partly responsibleaberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-Tdiscuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based

Keywords： cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

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exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CART-cells via TGF-β signaling

Frontiers of Medicine doi: 10.1007/s11684-023-1010-1

Abstract: exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CART-cells via TGF-β signaling

Keywords： exosomes induce activation     impair function CD19     exosomal CD19 antigen    

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Chimeric Antigen Receptors and Regulatory T Cells: The Potential for HLA-Specific Immunosuppression in Review

Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa

Engineering 2022, Volume 10, Issue 3,   Pages 30-43 doi: 10.1016/j.eng.2021.10.018

Abstract: Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specificbinding region within the synthetic CAR construct., and it is clear that such cells have greater accuracy, potency, and reduced off-target therapeuticIn contrast to conventional T cells (Tconvs), regulatory T cells (Tregs) play a major role in suppressingCAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,

Keywords： Chimeric antigen receptors     T cell     Treg     Alloimmunity     Bioengineering     Transplant     Autoimmunity    

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Quality Control and Nonclinical Research on CAR-T Cell Products: General Principles and Key Issues Review

Yonghong Li, Yan Huo, Lei Yu, Junzhi Wang

Engineering 2019, Volume 5, Issue 1,   Pages 122-131 doi: 10.1016/j.eng.2018.12.003

Abstract:

Adoptive cell therapy using chimeric antigen receptor T (CAR-T) cells, which is a promising cancerCAR-T cells are genetically modified T cells that can specifically recognize tumor specific antigensAt present, exciting results are being achieved in clinical applications of CAR-T cells for patientsThe research and development of CAR-T cells for various targets and for the treatment of solid tumorsthe general principles of and key issues regarding the quality control and nonclinical research of CAR-T

Keywords： Chimeric antigen receptor T cells     Quality control     Nonclinical research     Safety     Efficacy     Clinical    

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CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang

Frontiers of Medicine 2017, Volume 11, Issue 4,   Pages 554-562 doi: 10.1007/s11684-017-0543-6

Abstract:

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advancedWe successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity incell culture and in murine xenograft model, which is comparable to standard CAR-T cells.Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing

Keywords： CAR-T     CRISPR-Cas9     LAG-3    

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Innate and adaptive T cells in influenza disease

Simone Nüssing, Sneha Sant, Marios Koutsakos, Kanta Subbarao, Thi H.O. Nguyen, Katherine Kedzierska

Frontiers of Medicine 2018, Volume 12, Issue 1,   Pages 34-47 doi: 10.1007/s11684-017-0606-8

Abstract: cells and antibody-producing B cells) achieve viral clearance and host recovery.Adaptive T and B cells maintain immunological memory and provide protection against subsequent infectionsRecent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells)We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptiveCD8+ and CD4+ T cells, and discuss how these responses can be harnessed by novel

Keywords： influenza     innate T cells     CD4+ and CD8+ T cells     vaccination    

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γδ T cells in liver diseases

Xuefu Wang, Zhigang Tian

Frontiers of Medicine 2018, Volume 12, Issue 3,   Pages 262-268 doi: 10.1007/s11684-017-0584-x

Abstract:

γδ T cells display unique developmental, distributional, and functional patterns and canγδ T cells are enriched in the liver and exhibit liver-specific features.In this study, we review the properties of hepatic γδ T cells and summarize the roles ofγδ T cells in liver diseases.We believe that determining the properties and functions of γδ T cells in liver diseases

Keywords： γδT cells     liver infection     non-alcoholic fatty liver disease     autoimmune hepatitis     liver fibrosis and cirrhosis    

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Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

Frontiers of Medicine 2020, Volume 14, Issue 6,   Pages 701-710 doi: 10.1007/s11684-020-0763-z

Abstract: Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cellAlthough the identification of an ideal target antigen for AML is challenging, CAR T therapy remainsIn this review, we focus on the most recent and promising advances in CAR T therapies for AML.

Keywords： acute myeloid leukemia     CAR T     immunotherapy    

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High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

Frontiers of Medicine 2019, Volume 13, Issue 1,   Pages 69-82 doi: 10.1007/s11684-018-0677-1

Abstract:

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapyThe low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT).165 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cellsTCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered Tcells (TCR-Ts) in terms of interferon-g and granzyme B production

Keywords： cytokine-activated T cells     high-affinity T cell receptor     cancer immunotherapy     TCR-CAT    

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Regulatory T Cells and Their Clinical Applications in Antitumor Immunotherapy Review

Feng Xie, Rui Liang, Dan Li, Bin Li

Engineering 2019, Volume 5, Issue 1,   Pages 132-139 doi: 10.1016/j.eng.2018.12.002

Abstract:

Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cellsRegulatory T cells (Tregs) are a subgroup of suppressive CD4+ T cells that play a vital role in the maintenancegreat opportunities for improving antitumor efficiency in combination with other therapeutics (e.g., Car-T-based

Keywords： Regulatory T cells     Cancer     Immunotherapy    

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Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large

Frontiers of Medicine 2022, Volume 16, Issue 2,   Pages 285-294 doi: 10.1007/s11684-021-0843-8

Abstract: Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cellA single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of Tcells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory moleculeTen heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatmentThe overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively

Keywords： CAR-T cell therapy     refractory diffuse large B-cell lymphoma     cytokine release syndrome     dose-limiting    

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Engineered T Cell Therapies from a Drug Development Viewpoint Review

Fang Chen, Joseph A. Fraietta, Carl H. June, Zhongwei Xu, J. Joseph Melenhorst, Simon F. Lacey

Engineering 2019, Volume 5, Issue 1,   Pages 140-149 doi: 10.1016/j.eng.2018.11.010

Abstract: For example, T cells can be genetically modified to express chimeric antigen receptors (CARs), endowingback against persisting malignant cells.Anti-CD19 chimeric antigen receptor T cells (CART19) have demonstrated a remarkable degree of clinicalThis article reviews the use of biomarker-based assays to guide the optimization of CAR constructs, preclinicalAdvanced technologies and computational tools that enable the discovery of optimal targets, novel CAR

Keywords： Engineered T cell therapies     Chimeric antigen receptor     Drug development process     Biomarkers     CAR19    

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Management of cytokine release syndrome related to CAR-T cell therapy

Hongli Chen, Fangxia Wang, Pengyu Zhang, Yilin Zhang, Yinxia Chen, Xiaohu Fan, Xingmei Cao, Jie Liu, Yun Yang, Baiyan Wang, Bo Lei, Liufang Gu, Ju Bai, Lili Wei, Ruili Zhang, Qiuchuan Zhuang, Wanggang Zhang, Wanhong Zhao, Aili He

Frontiers of Medicine 2019, Volume 13, Issue 5,   Pages 610-617 doi: 10.1007/s11684-019-0714-8

Abstract: Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely usedsyndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cellsrefractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T

Keywords： chimeric antigen receptor T cell     cytokine release syndrome     tocilizumab    

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Title Author Date Type Operation

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

Journal Article

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

Journal Article

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

Journal Article

exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CART-cells via TGF-β signaling

Journal Article

Chimeric Antigen Receptors and Regulatory T Cells: The Potential for HLA-Specific Immunosuppression in

Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa

Journal Article

Quality Control and Nonclinical Research on CAR-T Cell Products: General Principles and Key Issues

Yonghong Li, Yan Huo, Lei Yu, Junzhi Wang

Journal Article

CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang

Journal Article

Innate and adaptive T cells in influenza disease

Simone Nüssing, Sneha Sant, Marios Koutsakos, Kanta Subbarao, Thi H.O. Nguyen, Katherine Kedzierska

Journal Article

γδ T cells in liver diseases

Xuefu Wang, Zhigang Tian

Journal Article

Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

Journal Article

High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

Journal Article

Regulatory T Cells and Their Clinical Applications in Antitumor Immunotherapy

Feng Xie, Rui Liang, Dan Li, Bin Li

Journal Article

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large

Journal Article

Engineered T Cell Therapies from a Drug Development Viewpoint

Fang Chen, Joseph A. Fraietta, Carl H. June, Zhongwei Xu, J. Joseph Melenhorst, Simon F. Lacey

Journal Article

Management of cytokine release syndrome related to CAR-T cell therapy

Hongli Chen, Fangxia Wang, Pengyu Zhang, Yilin Zhang, Yinxia Chen, Xiaohu Fan, Xingmei Cao, Jie Liu, Yun Yang, Baiyan Wang, Bo Lei, Liufang Gu, Ju Bai, Lili Wei, Ruili Zhang, Qiuchuan Zhuang, Wanggang Zhang, Wanhong Zhao, Aili He

Journal Article