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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 lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

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

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Immunoregulatory effects of

Dan Luo, Zhengyun Zuo, Hongyan Zhao, Yong Tan, Cheng Xiao

Frontiers of Medicine 2019, Volume 13, Issue 5, Pages 556-563 doi: 10.1007/s11684-018-0649-5

Abstract: treatment of rheumatoid arthritis, autoimmune diseases, and kidney disease due to their anti-inflammatory, immunoregulatoryHowever, the clinical immunoregulatory effects of TwHF and its extracts remain unclear, so we reviewedThis review provides a comprehensive summary of the recent literature on the immunoregulatory effects

Keywords： Tripterygium wilfordii Hook F immunoregulation clinical studies

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NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

Gang WANG

Frontiers of Medicine 2009, Volume 3, Issue 1, Pages 1-7 doi: 10.1007/s11684-009-0018-5

Abstract: Reactive oxygen species (ROS) are small molecule metabolites of oxygen that are prone to participate in redox reactions their high reactivity. Intracellular ROS could be generated in reduced nicotinamide-adenine dinucleotidephosphate (NADPH) oxidase-dependent and/or NADPH oxidase-independent manners. Physiologically, ROS are involved in many signaling cascades that contribute to normal processes. One classical example is that ROS derived from the NADPH oxidase and released in neurotrophils are able to digest invading bacteria. Excessive ROS, however, contribute to pathogenesis of various human diseases including cancer, aging, dimentia and hypertension. As signaling messengers, ROS are able to oxidize many targets such as DNA, proteins and lipids, which may be linked with tumor growth, invasion or metastasis. The present review summarizes recent advances in our comprehensive understanding of ROS-linked signaling pathways in regulation of tumor growth, invasion and metastasis, and focuses on the role of the NADPH oxidase-derived ROS in cancer pathogenesis.

Keywords： free radicals tumor phox cell proliferation cancer therapy

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Polymorphism of pharmaceutical molecules: perspectives on nucleation

Jie LU, Zhen LI, Xiaolin JIANG,

Frontiers of Chemical Science and Engineering 2010, Volume 4, Issue 1, Pages 37-44 doi: 10.1007/s11705-009-0294-2

Abstract: briefly introduces recent advances in the discovery and control of the polymorphs of pharmaceutical molecules

Keywords： development Polymorphism elucidation controversial relationship

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Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules

Yongqing Zhou, Xin Wang, Wei Zhang, Bo Tang, Ping Li

Frontiers of Chemical Science and Engineering 2022, Volume 16, Issue 1, Pages 4-33 doi: 10.1007/s11705-021-2041-2

Abstract: The interrelationships and synergistic regulations of bioactive molecules play pivotal roles in physiologicalTherefore, the simultaneous, accurate and timely detection of two bioactive molecules is crucial to exploreFluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactive molecules

Keywords： bioactive molecules fluorescent probes in living cells and in vivo review

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Chemical transdifferentiation: closer to regenerative medicine

Aining Xu,Lin Cheng

Frontiers of Medicine 2016, Volume 10, Issue 2, Pages 152-165 doi: 10.1007/s11684-016-0445-z

Abstract: Small molecules with compelling advantages are a potential alternative in manipulating cell fate conversionnature of cell transdifferentiation and summarize the current developments in the research of small molecules

Keywords： cell therapy cell transdifferentiation chemical compounds small molecules tissue regeneration