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Identification of novel HLA-A 0201-restricted epitopes from anterior gradient-2 as a tumor-associated antigen against colorectal cancer

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Cellular & Molecular Immunology 2012年第2期9卷 175-183页

作者： Hyun Ju lee Cheol Yi Hong Chun-Ji Jin Mi-Hyun Kim Youn-Kyung lee Thanh-Nhan Nguyen-Pham Hyunah lee Byoung Chul Park Ik-Joo Chung Hyeoung-Joon Kim je-jung lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun Hospital Hwasun Jeollanamdo Korea Department of Hematology-Oncology Chonnam National University Gwangju Korea VaxcelI-Bio Therapeutics Hwasun Jeollanamdo Korea Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea Korea Research Institute of Bioscience and Biotechnology （KRIBB） Daejeon Korea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National University Gwangiu Korea

Anterior gradient-2 （AGR2） promotes tumor growth, cell migration and cellular transformation and its enhanced expression is almost completely restricted to malignant tissues, thus making AGR2 an interesting target for the development of immunotherapeutic strategies. We investigated whether the AGR2 molecule comprises human leukocyte antigen （HLA）-A 0201-binding epitopes recognized by human cytotoxic T lymphocytes （CTLs）, which could be targeted in dendritic cell （DC）-based cancer immunotherapy against colorectal cancer （CRC）. We reviewed the sequence of AGR2 for peptides that could potentially bind to HLA-A 0201 with the aid of a computer-based program. Five candidate peptides with different binding scores were synthesized and tested. These peptides were then assessed for their immunogenicity to elicit specific immune responses mediated by CTLs in vitro by means of enzyme-linked immunospot assays and CTL assays. AGR2 was highly expressed in several CRC cell lines, including DK01, DLD1, KM 12C, HCT-8 and HT-29. DCs pulsed with AGR2-P2 （aa 11-19; LLVALSYTL） or AGR2-P4 （aa 127-135; RIMFVDPSL） generated potent CTLs that could lyse T2 cells pulsed with AGR2-P2 or AGR2-P4 and HLA-A0201＋ AGR2-positive CRC cell lines in a strong dose-dependent and HLA-A 0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC.

关键词： AGR2 colorectal cancer dendritic cell tumor-associated antigen

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Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model

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Cellular & Molecular Immunology 2021年第7期18卷 1652-1661页

作者： Jaya Lakshmi Thangaraj Seo-Yeon Ahn Sung-Hoon jung Manh-Cuong Vo Tan-Huy Chu Minh-Trang Thi Phan Minsuk Kwon Kyung-Hwa lee Mihee Kim Ga-Young Song Deok-Hwan Yang Jae-Sook Ahn Hyeoung-Joon Kim Duck Cho je-jung lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun Hospital and Chonnam National University Medical SchoolGwangjuKorea Department of Hematology-Oncology Chonnam National University Hwasun Hospital and Chonnam National University Medical SchoolGwangjuKorea Department of Molecular Medicine Chonnam National UniversityGwangjuKorea Stem Cell&Regenerative Medicine Institute Samsung Medical CenterSeoulKorea View author publications Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Pathology Chonnam National University Medical SchoolGwangjuKorea Department of Health Sciences and Technology SAIHSTSungkyunkwan UniversitySeoulKorea Department of Laboratory Medicine and Genetics Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea

The use of natural killer(NK)cells is a promising and safe immunotherapeutic approach in the field of cancer ***,combination treatments are required to enhance the effector functions and therapeutic efficacy of NK *** this study,we investigated the potential of daratumumab(Dara),bortezomib,and dexamethasone(Dvd)to augment the antitumor effects of NK cells in a multiple myeloma(MM)xenograft mouse *** cells were expanded and activated using the K562-OX40 ligand and membrane-bound IL-18 and IL-21 in the presence of IL-2 and IL-15 from peripheral blood mononuclear cells from MM patients.A human MM xenograft model was established using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull(NSG)***-bearing mice were divided into six treatment groups:no treatment,expanded NK cells(eNKs),Dara,Dara+eNKs,Dvd,and Dvd+*** treatment strongly enhanced the cytotoxicity of eNKs by upregulating expression of NK cell activation ligands,downregulating expression of NK cell inhibitory ligands,and promoting antibody-dependent cellular *** combination of eNKs with Dvd significantly prolonged mouse survival and reduced the tumor burden and serum M-protein ***,Dvd pretreatment significantly increased eNK persistence and homing to MM *** findings suggest that Dvd treatment potentiates the antimyeloma effects of NK cells expanded and activated ex vivo by modulating immune responses in MM-bearing mice.

关键词： Multiple myeloma Natural killer cell Chemotherapy

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Optimal culture conditions for the generation of natural killer cell-induced dendritic cells for cancer immunotherapy

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Cellular & Molecular Immunology 2012年第1期9卷 45-53页

作者： Thanh-Nhan Nguyen-Pham Deok-Hwan Yang Truc-Anh Thi Nguyen Mi-Seon Lim Cheol Yi Hong Mi-Hyun Kim Hyun Ju lee Youn-Kyung lee Duck Cho Soo-Young Bae Jae-Sook Ahn Yeo-Kyeoung Kim Ik-Joo Chung Hyeoung-Joon Kim je-jung lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun HospitalJeollanamdoKorea Department of Hematology-Oncology Chonnam National University Hwasun HospitalJeollanamdoKorea Vaxcell-Bio Therapeutics JeollanamdoKorea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National UniversityGwangjuKorea

Dendritic cell(DC)-based vaccines continue to be considered an attractive tool for cancer *** require an additional signal from the environment or other immune cells to polarize the development of immune responses toward T helper 1(Th1)or Th2 *** play a role in natural killer(NK)cell activation,and NK cells are also able to activate and induce the maturation of *** investigated the types of NK cells that can induce the maturation and enhanced function of DCs and the conditions under which these interactions *** that were activated by resting NK cells in the presence of inflammatory cytokines exhibited increased expression of several costimulatory molecules and an enhanced ability to produce *** cell-stimulated DCs potently induced Th1 polarization and exhibited the ability to generate tumor antigen-specific cytotoxic T lymphocyte *** data demonstrate that functional DCs can be generated by coculturing immature DCs with freshly isolated resting NK cells in the presence of Toll-like receptor agonists and proinflammatory cytokines and that the resulting DCs effectively present antigens to induce tumor-specific T-cell responses,which suggests that these cells may be useful for cancer immunotherapy.

关键词： cancer immunotherapy dendritic cells natural killer cells signal

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Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists

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Cellular & Molecular Immunology 2011年第4期8卷 341-347页

作者： Thanh-Nhan Nguyen-Pham Mi-Seon Lim Truc Anh Thi Nguyen Youn-Kyung lee Chun-Ji Jin Hyun Ju lee Cheol Yi Hong Jae-Sook Ahn Deok-Hwan Yang Yeo-Kyeoung Kim Ik-Joo Chung Byoung Chul Park Hyeoung-Joon Kim je-jung lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun HospitalJeollanamdoKorea Department of Hematology-Oncology Chonnam National UniversityGwangjuKorea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National UniversityGwangjuKorea Vaxcell-Bio Therapeutics JeollanamdoKorea Korea Research Institute of Bioscience and Biotechnology(KRIBB) DaejeonKorea

The major limitation for the maturation of dendritic cells(DCs)using Toll-like receptor(TLR)agonists is their decreased ability to migrate into lymph nodes compared with conventional ***38 can be used as a multifunctional marker to modulate migration,survival and Th1 responses of ***74 has been shown to negatively regulate DC *** goal of this study was to investigate the combinations of TLR agonists and interferons(IFNs)that most effectively regulate CD38 and CD74 expression on *** TLR agonist stimulation in combination with IFN-a and IFN-c was the best method for regulating CD38 and CD74 expression and inducing the highest secretion of *** in vitro migration assay showed that DCs treated with this combination had significantly enhanced migratory ability,similar to that observed in cells expressing CD38,CD74 and *** results of this study suggest that an alternative maturation protocol in which two TLR ligands are combined with type I and II IFNs generates potent DCs that have both a high migratory capacity and high IL-12p70 production.

关键词： CD38 CD74 dendritic cells interferon Toll-like receptor

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Adverse effects of early-life stress:focus on the rodent neuroendocrine system

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Neural Regeneration Research 2024年第2期19卷 336-341页

作者： Seung Hyun lee Eui-Man jung Department of Molecular Biology College of Natural SciencesPusan National UniversityBusanRepublic of Korea

Early-life stress is associated with a high prevalence of mental illnesses such as post-traumatic stress disorders,attention-deficit/hyperactivity disorder,schizophrenia,and anxiety or depressive behavior,which constitute major public health *** the early stages of brain development after birth,events such as synaptogenesis,neuron maturation,and glial differentiation occur in a highly orchestrated manner,and external stress can cause adverse long-term effects throughout *** body utilizes multifaceted mechanisms,including neuroendocrine and neurotransmitter signaling pathways,to appropriately process external *** individuals first exposed to early-life stress deploy neurogenesis as a stress-defense mechanism;however,in adulthood,early-life stress induces apoptosis of mature neurons,activation of immune responses,and reduction of neurotrophic factors,leading to anxiety,depression,and cognitive and memory *** process involves the hypothalamus-pituitary-adrenal axis and neurotransmitters secreted by the central nervous system,including norepinephrine,dopamine,and *** rodent early-life stress model is generally used to experimentally assess the effects of stress during *** paper reviews the use of the early-life stress model and stress response mechanisms of the body and discusses the experimental results regarding how early-life stress mediates stress-related pathways at a high vulnerability of psychiatric disorder in adulthood.

关键词： early-life stress hypothalamic-pituitary-adrenergic axis maternal separation mental illness neurodevelopmental disorder neuroendocrine system neurotransmitter

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A combination of immunoadjuvant nanocomplexes and dendritic cell vaccines in the presence of immune checkpoint blockade for effective cancer immunotherapy

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Cellular & Molecular Immunology 2021年第6期18卷 1599-1601页

作者： Manh-Cuong Vo Seo-Yeon Ahn Tan-Huy Chu Saji Uthaman Shammer Pillarisetti Tung Nguyen Thanh Uong Thangaraj Jaya Lakshmi Mihee Kim Ga-Young Song Sung-Hoon jung Deok-Hwan Yang Jae-Sook Ahn Hyeoung-Joon Kim In-Kyu Park je-jung lee Institute of Research and Development Duy Tan UniversityDanangVietnam Research Center for Cancer Immunotherapy Chonnam National University Hwasun HospitalHwasunJeollanamdoRepublic of Korea Department of Hematology-Oncology Chonnam National University Hwasun HospitalChonnam National University Medical SchoolGwangjuRepublic of Korea Department of Polymer Science and Engineering Chungnam National UniversityDaejeonRepublic of Korea Department of Biomedical Science Chonnam National University Medical SchoolGwangjuRepublic of Korea Department of Radiation Oncology Chonnam National University Hwasun HospitalChonnam National University Medical SchoolGwangjuSouth Korea View author publications

Nanovaccines are used as delivery platforms for antigens and adjuvants, which activate antigen-presenting cells (APCs) and enhance anticancer immune responses.1,2 Researchers have recently developed a self-assembled nanocomplex using a polysorbitol-co-PEI (PSPEI) polymer complexed with poly(I:C) (PIC). By binding to different surface proteins, this nanocomplex enhances the intracellular delivery of cargos and induces potent anticancer immune responses against melanoma cells.3 We have previously demonstrated that PD-1/PD-L1 blockade enhanced the efficacy of DC-based cancer immunotherapy.4,5 Moreover, the combination of nanomedicines and PD-L1 blockade has been reported to enhance CD8+ T cell activation and inhibit immunosuppressive cells within the tumor microenvironment.6 In the present study, we investigated the therapeutic efficacy of a combinatorial treatment comprising the immunoadjuvant nanocomplex PSPEI-PIC, a DC vaccine, and PD-L1 blockade in a murine colon cancer model.

关键词： adjuvant vaccines immunotherapy

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In situ infrared, Raman and X-ray spectroscopy for the mechanistic understanding of hydrogen evolution reaction

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Journal of Energy Chemistry 2024年第3期90卷 632-651,I0014页

作者： Andi Haryanto Kyounghoon jung Chan Woo lee Dong-Wan Kim Department of Chemistry Kookmin UniversitySeoul 02707Republic of Korea School of Civil Environmental and Architectural EngineeringKorea UniversitySeoul 02841Republic of Korea

Hydrogen production by water reduction reactions has received considerable attention because hydrogen is considered a clean-energy carrier,key for a sustainable energy *** methods have been widely used to study the reaction mechanism of the hydrogen evolution reaction(HER),but the calculation results need to be supported by experimental results and direct evidence to confirm the mechanistic *** this review,we discuss the fundamental principles of the in situ spectroscopic strategy and a theoretical model for a mechanistic understanding of the *** addition,we investigate recent studies by in situ Fourier transform infrared(FTIR),Raman spectroscopy,and X-ray absorption spectroscopy(XAS) and cover new findings that occur at the catalyst-electrolyte interface during *** spectroscopic strategies provide practical ways to elucidate catalyst phase,reaction intermediate,catalyst-electrolyte interface,intermediate binding energy,metal valency state,and coordination environment during HER.

关键词： Hydrogen evolution reaction Infrared spectroscopy Raman spectroscopy X-ray absorption spectroscopy Reaction mechanism

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Self-assembly of tau fragments as a key pathologic event in tauopathies

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Neural Regeneration Research 2024年第12期19卷 2565-2566页

作者： Ly Thi Huong Luu Le jung Hoon lee Min Jae lee Department of Biochemistry and Molecular Biology Seoul National University College of MedicineSeoulKorea

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the *** has unique biophysical properties that make it both highly water-soluble and positively *** tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

关键词： tau pathologic assembly

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Artificial optoelectronic synapse based on spatiotemporal irradiation to source-sharing circuitry of synaptic phototransistors

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InfoMat 2024年第2期6卷 131-141页

作者： Seungho Song Changsoon Choi Jongtae Ahn je-Jun lee Jisu Jang Byoung-Soo Yu jung Pyo Hong Yong-Sang Ryu Yong-Hoon Kim Do Kyung Hwang Center for Opto-Electronic Materials and Devices Post-Silicon Semiconductor InstituteKorea Institute of Science and Technology(KIST)SeoulRepublic of Korea School of Advanced Materials Science and Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Center for Spintronics Post-Silicon Semiconductor InstituteKorea Institute of Science and Technology(KIST)SeoulRepublic of Korea Division of Nanoscience&Technology KIST SchoolUniversity of Science and Technology(UST)SeoulRepublic of Korea School of Biomedical Engineering Korea UniversitySeoulRepublic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoulRepublic of Korea

To overcome the intrinsic inefficiency of the von Neumann architecture,neuromorphic devices that perform analog vector–matrix multiplication have been highlighted for achieving power-and time-efficient data *** particular,artificial synapses,of which conductance should be programmed to represent the synaptic weights of the artificial neural network,have been intensively researched to realize neuromorphic ***,inspired by excitatory and inhibitory synapses,we develop an artificial optoelectronic synapse that shows both potentiation and depression characteristics triggered only by optical *** design of the artificial optoelectronic synapse,in which excitatory and inhibitory synaptic phototransistors are serially connected,enables these characteristics by spatiotemporally irradiating the phototransistor channels with optical ***,a negative synaptic weight can be realized without the need for electronic components such as *** such attributes,the artificial optoelectronic synapse is demonstrated to classify three digits with a high recognition rate(98.3%)and perform image preprocessing via analog vector-matrix multiplication.

关键词： amorphous oxide semiconductor analog processing artificial synapse neuromorphic optoelectronics

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Effect of Farnesyl Caffeate-Induced Apoptosis of Lung Carcinoma Cell Line from Damage to DNA

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Pharmacology & Pharmacy 2013年第9期4卷 689-695页

作者： Kyu Sik Kim Akemi Umeyama Toshihiro Hashimoto Hyun-Ju Cho je-jung lee Masao Takei Department of Pulmonary Medicine Chonnam National University Medical School Gwangiu South Korea Department of Pulmonary Medicine Chonnam National University Medical School Gwangiu South Korea Faculty of Pharmaceutical Sciences Tokushima University Tokushima Japan Research Center for Cancer Immunotherapy Chonnam National University Hwasun Hospital Hwasun-eup Hwasun-gun South Korea Research Center for Cancer Immunotherapy Chonnam National University Hwasun Hospital Hwasun-eup Hwasun-gun South Korea Department of Hematology-Oncology Chonnam National University Medical School Gwangiu South Korea.

Farnesyl caffeate, synthesis of propolis and polar bud excretion, has been reported to exhibit anti-allergic effects in mice. However, little is known about anti-tumor effects. In this study, we investigated the effect of Farnesyl caffeate in cell proliferation of lung carcinoma cell line (H157). Antiproliferative effect and apoptosis on H157 cell were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) and DNA fragmentation assay, respectively. Farnesyl caffeate inhibited the growth of H157 cell in dose-dependent manner. Morphological changes of nuclei by staining Hoechst 33258 and DNA fragmentation suggested that Farnesyl caffeate induced death involved in a mechanism of apoptosis. Moreover, caspase-3, caspase-7 and caspase-9 were activated by Farnesyl caffeate on H157 cell. The protein expressions of Bax and Bcl-2 were down-regulated by Farnesyl caffeate, resulting in cytochrome c release from the mitochondria. Farnesyl caffeate significantly increased the expression of p53 proteins which indicates that p53 plays a pivotal role in the initiation phase of Farnesyl caffeate-induced HepG2 cell apoptosis. These results demonstrated Farnesyl caffeate-induced apoptosis in human lung carcinoma cell line. More detailed mechanism of ?Farnesyl caffeate-induced H157 apoptosis remains to be elucidated.

关键词： Apoptosis Propolis Farnesyl Caffeate DNA Fragmentation Lung Cancer

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