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  1. Article ; Online: Fc receptor-like 5 (FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma

    Zhengyu Yu / Hexian Li / Qizhong Lu / Zongliang Zhang / Aiping Tong / Ting Niu

    Signal Transduction and Targeted Therapy, Vol 9, Iss 1, Pp 1-

    2024  Volume 14

    Abstract: Abstract Multiple myeloma (MM) remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell (CAR-T) therapy. Current targets of CAR-T cells used in MM immunotherapy have limitations, with a subset of patients ... ...

    Abstract Abstract Multiple myeloma (MM) remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell (CAR-T) therapy. Current targets of CAR-T cells used in MM immunotherapy have limitations, with a subset of patients experiencing antigen loss resulting in relapse. Therefore, novel targets for enhancing CAR-T cell therapy in MM remain needed. Fc receptor-like 5 (FCRL5) is a protein marker with considerably upregulated expression in MM and has emerged as a promising target for CAR-T cell therapeutic interventions, offering an alternative treatment for MM. To further explore this option, we designed FCRL5-directed CAR-T cells and assessed their cytotoxicity in vitro using a co-culture system and in vivo using MM cell-derived xenograft models, specifically focusing on MM with gain of chromosome 1q21. Given the challenges in CAR-T therapies arising from limited T cell persistence, our approach incorporates interleukin-15 (IL-15), which enhances the functionality of central memory T (TCM) cells, into the design of FCRL5-directed CAR-T cells, to improve cytotoxicity and reduce T-cell dysfunction, thereby promoting greater CAR-T cell survival and efficacy. Both in vitro and xenograft models displayed that FCRL5 CAR-T cells incorporating IL-15 exhibited potent antitumor efficacy, effectively inhibiting the proliferation of MM cells and leading to remarkable tumor suppression. Our results highlight the capacity of FCRL5-specific CAR-T cells with the integration of IL-15 to improve the therapeutic potency, suggesting a potential novel immunotherapeutic strategy for MM treatment.
    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Targeted protein degradation

    Lin Zhao / Jia Zhao / Kunhong Zhong / Aiping Tong / Da Jia

    Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-

    mechanisms, strategies and application

    2022  Volume 13

    Abstract: Abstract Traditional drug discovery mainly focuses on direct regulation of protein activity. The development and application of protein activity modulators, particularly inhibitors, has been the mainstream in drug development. In recent years, ... ...

    Abstract Abstract Traditional drug discovery mainly focuses on direct regulation of protein activity. The development and application of protein activity modulators, particularly inhibitors, has been the mainstream in drug development. In recent years, PROteolysis TArgeting Chimeras (PROTAC) technology has emerged as one of the most promising approaches to remove specific disease-associated proteins by exploiting cells’ own destruction machinery. In addition to PROTAC, many different targeted protein degradation (TPD) strategies including, but not limited to, molecular glue, Lysosome-Targeting Chimaera (LYTAC), and Antibody-based PROTAC (AbTAC), are emerging. These technologies have not only greatly expanded the scope of TPD, but also provided fresh insights into drug discovery. Here, we summarize recent advances of major TPD technologies, discuss their potential applications, and hope to provide a prime for both biologists and chemists who are interested in this vibrant field.
    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Development of therapeutic antibodies for the treatment of diseases

    Zeng Wang / Guoqing Wang / Huaqing Lu / Hongjian Li / Mei Tang / Aiping Tong

    Molecular Biomedicine, Vol 3, Iss 1, Pp 1-

    2022  Volume 31

    Abstract: Abstract Since the first monoclonal antibody drug, muromonab-CD3, was approved for marketing in 1986, 165 antibody drugs have been approved or are under regulatory review worldwide. With the approval of new drugs for treating a wide range of diseases, ... ...

    Abstract Abstract Since the first monoclonal antibody drug, muromonab-CD3, was approved for marketing in 1986, 165 antibody drugs have been approved or are under regulatory review worldwide. With the approval of new drugs for treating a wide range of diseases, including cancer and autoimmune and metabolic disorders, the therapeutic antibody drug market has experienced explosive growth. Monoclonal antibodies have been sought after by many biopharmaceutical companies and scientific research institutes due to their high specificity, strong targeting abilities, low toxicity, side effects, and high development success rate. The related industries and markets are growing rapidly, and therapeutic antibodies are one of the most important research and development areas in the field of biology and medicine. In recent years, great progress has been made in the key technologies and theoretical innovations provided by therapeutic antibodies, including antibody–drug conjugates, antibody-conjugated nuclides, bispecific antibodies, nanobodies, and other antibody analogs. Additionally, therapeutic antibodies can be combined with technologies used in other fields to create new cross-fields, such as chimeric antigen receptor T cells (CAR-T), CAR-natural killer cells (CAR-NK), and other cell therapy. This review summarizes the latest approved or in regulatory review therapeutic antibodies that have been approved or that are under regulatory review worldwide, as well as clinical research on these approaches and their development, and outlines antibody discovery strategies that have emerged during the development of therapeutic antibodies, such as hybridoma technology, phage display, preparation of fully human antibody from transgenic mice, single B-cell antibody technology, and artificial intelligence-assisted antibody discovery.
    Keywords Immunotherapy ; Antibody drugs ; Phage display libraries ; Transgenic mice ; Single B-cell ; AI-assisted antibody discovery ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Springer
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: SARS‐CoV‐2 spike protein harnesses SNX27‐mediated endocytic recycling pathway

    Lin Zhao / Kunhong Zhong / Jia Zhao / Xin Yong / Aiping Tong / Da Jia

    MedComm, Vol 2, Iss 4, Pp 798-

    2021  Volume 809

    Abstract: Abstract SARS‐CoV‐2 is an enveloped positive‐sense RNA virus that depends on host factors for all stages of its life. Membrane receptor ACE2 is a well‐established factor for SARS‐CoV‐2 docking. In addition to ACE2, whole‐genome genetic screens have ... ...

    Abstract Abstract SARS‐CoV‐2 is an enveloped positive‐sense RNA virus that depends on host factors for all stages of its life. Membrane receptor ACE2 is a well‐established factor for SARS‐CoV‐2 docking. In addition to ACE2, whole‐genome genetic screens have identified additional proteins, such as endosomal trafficking regulators SNX27 and retromer, as key host factors required for SARS‐CoV‐2 infection. However, it is poorly understood how SARS‐CoV‐2 utilize host endocytic transport pathways to produce productive infection. Here, we report that SNX27 interacts with the SARS‐CoV‐2 spike (S) protein to facilitate S protein surface expression. Interestingly, S protein binds to the PDZ domain of SNX27, although it does not contain a PDZ‐binding motif (PDZbm). Either abrogation of the SNX27 PDZ domain or S protein “MTSC” motif, which is critical for SNX27 binding, decreases surface expression of S protein and viral production. Collectively, our study highlights a novel approach utilized by SARS‐CoV‐2 to facilitate virion trafficking to establish virus infection.
    Keywords endocytic trafficking ; endosome ; host–pathogen interaction ; S protein ; SARS‐CoV‐2 ; Medicine ; R
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Potential of SARS-CoV-2 to Cause CNS Infection

    Jianhan Huang / Meijun Zheng / Xin Tang / Yaxing Chen / Aiping Tong / Liangxue Zhou

    Frontiers in Neurology, Vol

    Biologic Fundamental and Clinical Experience

    2020  Volume 11

    Abstract: SARS-CoV-2 is a novel coronavirus leading to serious respiratory disease and is spreading around the world at a raging speed. Recently there is emerging speculations that the central nervous system (CNS) may be involved during SARS-CoV-2 infection, ... ...

    Abstract SARS-CoV-2 is a novel coronavirus leading to serious respiratory disease and is spreading around the world at a raging speed. Recently there is emerging speculations that the central nervous system (CNS) may be involved during SARS-CoV-2 infection, contributing to the respiratory failure. However, the existence of viral replication in CNS has not been confirmed due to the lack of evidence from autopsy specimens. Considering the tropism of SARS-CoV-2, ACE2, is prevailing in CNS, and the neuro-invasive property of human coronavirus was widely reported, there is a need to identified the possible complications during COVID-19 for CNS. In this review, we conduct a detailed summary for the potential of SARS-CoV-2 to infect central nervous system from latest biological fundamental of SARS-CoV-2 to the clinical experience of other human coronaviruses. To confirm the neuro-invasive property of SARS-CoV-2 and the subsequent influence on patients will require further exploration by both virologist and neurologist.
    Keywords COVID-19 ; human coronavirus ; SARS-CoV-2 ; central nervous system ; viral infection ; Neurology. Diseases of the nervous system ; RC346-429 ; covid19
    Subject code 572
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Antimicrobial peptide DP7 with potential activity against SARS coronavirus infections

    Rui Zhang / Xiaohua Jiang / Jingxin Qiao / Zeng Wang / Aiping Tong / Jinliang Yang / Shengyong Yang / Li Yang

    Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-

    2021  Volume 3

    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Administration of B7-H3 targeted chimeric antigen receptor-T cells induce regression of glioblastoma

    Xin Tang / Yuelong Wang / Jianhan Huang / Zongliang Zhang / Fujun Liu / Jianguo Xu / Gang Guo / Wei Wang / Aiping Tong / Liangxue Zhou

    Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-

    2021  Volume 3

    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: DCLK1 autoinhibition and activation in tumorigenesis

    Linna Cheng / Zejing Yang / Wenhao Guo / Chengyong Wu / Shufang Liang / Aiping Tong / Zhongwei Cao / Rick F. Thorne / Sheng-Yong Yang / Yamei Yu / Qiang Chen

    The Innovation, Vol 3, Iss 1, Pp 100191- (2022)

    2022  

    Abstract: Doublecortin-like kinase 1 (DCLK1) is upregulated in many tumors and is a marker for tumor stem cells. Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy. However, the regulation of DCLK1 kinase activity is poorly ...

    Abstract Doublecortin-like kinase 1 (DCLK1) is upregulated in many tumors and is a marker for tumor stem cells. Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy. However, the regulation of DCLK1 kinase activity is poorly understood, particularly the function of its autoinhibitory domain (AID), and, moreover, no physiological activators of DCLK1 have presently been reported. Here we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of DCLK1. The C-terminal AID functions to block the ATP-binding site and is competitive with ATP. HPCAL1 binds directly to the AID in a Ca2+-dependent manner, which releases the autoinhibition. We also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity upregulation. Our results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.
    Keywords kinase ; DCLK1 ; autoinhibition ; HPCAL1 ; tumorigenesis ; Science (General) ; Q1-390
    Subject code 572
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: GEF-independent Ran activation shifts a fraction of the protein to the cytoplasm and promotes cell proliferation

    Jinhan Zhou / Yuping Tan / Yuqing Zhang / Aiping Tong / Xiaofei Shen / Xiaodong Sun / Da Jia / Qingxiang Sun

    Molecular Biomedicine, Vol 1, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Abstract Ran (Ras-related nuclear protein) plays several important roles in nucleo-cytoplasmic transport, mitotic spindle formation, nuclear envelope/nuclear pore complex assembly, and other functions in the cytoplasm, as well as in cellular ... ...

    Abstract Abstract Ran (Ras-related nuclear protein) plays several important roles in nucleo-cytoplasmic transport, mitotic spindle formation, nuclear envelope/nuclear pore complex assembly, and other functions in the cytoplasm, as well as in cellular transformation when switched on. Unlike other members of the GTPase superfamily, Ran binds more tightly to GDP than to GTP due to the presence of an auto-inhibitory C-terminal tail. Multiple missense mutations in the C-terminus of Ran occur in cancers, but their biological significance remains unclear. Here, the quantitative GDP/GTP binding preference of four engineered mutations with unstable C-termini was analyzed using a devised mant-GDP dissociation assay. The results showed that the impact of different C-terminal mutations depends on multiple factors. Although these mutants were more GTP-loaded in human cells, they were shown to be more cytoplasmic, and to support nuclear transport with minimally or partially reduced efficiency. Further, several Ran cancer mutants were compromised in autoinhibition, slightly more GTP-bound, more cytoplasmic, and enhanced the proliferation of A549 and HeLa cells in vitro. Thus, our work reveals a new route of Ran activation independent of guanine nucleotide exchange factor (GEF), which may account for the hyper-proliferation induced by Ran cancer mutations.
    Keywords Small GTPases ; Nuclear transport ; GTP bias ; Activation ; Cancer mutations ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Springer
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Molecular basis of the lipid-induced MucA-MucB dissociation in Pseudomonas aeruginosa

    Tao Li / Lihui He / Changcheng Li / Mei Kang / Yingjie Song / Yibo Zhu / Yalin Shen / Ninglin Zhao / Chang Zhao / Jing Yang / Qin Huang / Xingyu Mou / Aiping Tong / Jinliang Yang / Zhenling Wang / Chengjie Ji / Hong Li / Hong Tang / Rui Bao

    Communications Biology, Vol 3, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: Tao Li et al. report crystal structure of MucA-MucB complex and identify a cavity region of MucB that binds PEG molecule. They further show that this hydrophobic cavity of MucB is a primary site for sensing lipid molecules and that lipid A stimulates ... ...

    Abstract Tao Li et al. report crystal structure of MucA-MucB complex and identify a cavity region of MucB that binds PEG molecule. They further show that this hydrophobic cavity of MucB is a primary site for sensing lipid molecules and that lipid A stimulates MucB to release MucA for AlgW cleavage, helping to understand the regulation mechanism of alginate biosynthesis.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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