• Title/Summary/Keyword: Anti-E2 antibody

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Immune Checkpoint Inhibitors in 10 Years: Contribution of Basic Research and Clinical Application in Cancer Immunotherapy

  • Jii Bum Lee;Hye Ryun Kim;Sang-Jun Ha
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.2.1-2.22
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    • 2022
  • Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.

Study of the effect of Woohwangporhyonghwan (minus REALGAR and CINNABARIS) and Saengnyosamultang on the Anti-allergic in rats and mice (우황포룡환(牛黃抱龍丸) 거웅황주사방(去雄黃朱砂方) 및 생뇨사물탕(生料四物湯)의 항(抗)알레르기에 관(關)한 실험적(實驗的) 연구(硏究))

  • Choe Chang-Gyu;Park Eun-Jeong;Jeong Gyu-Man
    • The Journal of Pediatrics of Korean Medicine
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    • v.7 no.1
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    • pp.1-16
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    • 1993
  • Experimental studies were done to research the clinical effect of Woohwangporhyonghwan(minus REALGAR and CINNABARIS) and Saengnyosamultang on the Anti-allergie effect in rats and mice. The results obtained as follows: 1. (1) In the effects of Woohwangporhyonghwan(minus REALGAR and CINNABARIS) and Saengnyosamultang on vascular permeability responses to intradermal histamin in rats, Woohwangporhyonghwan(minus REALGAR and CINNABARIS) and Saengnyosamultang revealed significant effect. (2) In the effects of Woohwangporhyonghwan(minus REALGAR and CINNABARIS) and Saengnyosamultang on vascular permeability responses to intradermal serotonin in rats, Woohwangporhyonghwan(minus REALGAR and CINNABARIS) revealed significant effect. 2. In the 48 hour homologous passive cutaneous anaphylaxis in rats provoked by the Ig E-like antibody against egg albumin, Woohwangporhyonghwan(minus REALGAR and CINNABARIS) and Saengnyosamultang revealed significant effect. 3. In the delayed type hypersensitivity responses to picryl chloride in mice, Woohwangporhyonghwan(minus REALGAR and CINNABARIS) revealed significant effect. 4. In the delayed type hypersensitivity responses to SRBC(Sheep Red Blood cell) in mice, Woohwangporhyonghwan(minus REALGAR and CINNABARIS) and Saengnyosamultang revealed significant effect. According to above-stated results, Woohwangporhyonghwan(minus REALGAR and CINNABARIS) and Saengnyosamultang were concluded to be effective as anti-allergic regimen and recommended to be used for treatment of allergic diseases.

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Overlap syndrome of Miller-Fisher syndrome/Pharyngeal-Cervical-Brachial variant-Guillain Barre Syndrome with anti-ganglioside complex antibodies

  • Lee, Suk-yoon;Oh, Seong-il;Huh, So-Young;Shin, Kyong Jin;Kim, Jong Kuk;Yoon, Byeol-A
    • Annals of Clinical Neurophysiology
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    • v.22 no.2
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    • pp.112-116
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    • 2020
  • Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) can present with overlapping features. A 56-year-old female developed ptosis and diplopia after an upper respiratory infection, and presented with facial palsy, dysarthria, brachial weakness, ataxia, and areflexia. Mild weakness of both legs appeared after a few days. Anti-ganglioside complex antibody were positive to IgG GM1/GQ1b and GQ1b/sulfatide antibodies. The present case suggests that the manifestation of overlap between MFS/PCB variants and GBS could be caused by antiganglioside complex antibodies.

Immunochemical Studies of Starfish Gangliosides: Production of Monoclonal Antibody against AG-2, the Major Ganglioside of Starfish Acanthaster planci, and Detecting Its Distribution in Tissues by TLC Immunostaining

  • Miyamoto, Tomofumi;Yamamoto, Atsushi;Sakai, Maki;Tanaka, Hiroyuki;Shoyama, Yukihiro;Higuchi, Ryuichi
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.4
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    • pp.298-304
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    • 2006
  • In this study, we establish a thin-layer chromatography (TLC) immunostaining method for detecting starfish gangliosides. A new monoclonal antibody (MAb) against AG-2, the major gangliosides molecular species of Acanthaster planci, was produced by fusing hybridoma with splenocytes immunized to liposomal AG-2. BALB/c male mice were injected with liposomal AG-2 antigen, and immunized. Their splenocytos were isolated and fused with hypoxanthine-aminopterine-thimidine (HAT)-sensitive mouse myeloma cells. Hybridomas producing MAb reactive to AG-2 were cloned using the limited dilution method. Established hybridomas were cultured in eRDF medium. Crude MAb produced from clone 8D4 was purified with a magnesium pyrophosphate column. Enzyme immunoassay and TLC immunostaining of AG-2 were performed using the purified MAb. Structurally related gangliosides did not cross-react with anti-AG-2 antibodies. The detection limit of TLC immunostaining was 50 ng of AG-2. The newly established immunostaining method was further developed for detecting AG-2 distribution and qualitative analysis in tissues and/or organs. Our results show that the majority of AG-2 is present in the stomach of male A. planci, while AG-2 is distributed not only in the stomach but also in the the pyloric caeca of female A. planci.

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Definition of the peptide mimotope of cellular receptor for hepatitis C virus E2 protein using random peptide library (Random peptide library를 이용한 C형 간염바이러스 E2 단백질 세포막 수용체의 peptide mimotope 규명)

  • Lee, In-Hee;Paik, Jae-Eun;Seol, Sang-Yong;Seog, Dae-Hyun;Park, Sae-Gwang;Choi, In-Hak
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.77-86
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    • 2001
  • Background: Hepatitis C virus(HCV), a family of Flaviviridae, has a host cell-derived envelope containing a positive-stranded RNA genome, and has been known as the maj or etiological agent for chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. There remains a need to dissect a molecular mechanism of pathogenesis for the development of therapeutic and effective preventive measure for HCV. Identification of cellular receptor is of central importance not only to understand the viral pathogenesis, but also to exploit strategies for prevention of HCV. This study was aimed at identifying peptide mimotopes inhibiting the binding of E2 protein of HCV to MOLT-4 cell. Methods: In this study, phage peptide library displaying a random peptides consisting of 7 or 12 random peptides was employed in order to pan against E2 protein. Free HCV particles were separated from the immune complex forms by immunoprecipitation using anti-human IgG antibody, and used for HCV-capture ELISA. To identify the peptides inhibiting E2-binding to MOLT-4 cells, E2 protein was subj ect to bind to MOLT-4 cells under the competition with phage peptides. Results: Several phage peptides were selected for their specific binding to E2 protein, which showed the conserved sequence of SHFWRAP from 3 different peptide sequences. They were also able to recognize the HCV particles in the sera of HCV patients captured by monoclonal antibody against E2 protein. Two of them, showing peptide sequence of HLGPWMSHWFQR and WAPPLERSSLFY respectively, were revealed to inhibit the binding of E2 protein to MOLT-4 cell efficiently in dose dependent mode. However, few membrane-associated receptor candidates were seen using Fasta3 programe for homology search with these peptides. Conclusion: Phage peptides containing HLGPWMSHWFQR and WAPPLERSSLFY respectively, showed the inhibition of E2-binding to MOLT-4 cells. However, they did not reveal any homologues to cellular receptors from GenBank database. In further study, cellular receptor could be identified through the screening of cDNA library from MOLT-4 or hepatocytes using antibodies against these peptide mimotopes.

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Recent Progress in Immunotherapy for Gastric Cancer

  • Jeesun Yoon;Tae-Yong Kim;Do-Youn Oh
    • Journal of Gastric Cancer
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    • v.23 no.1
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    • pp.207-223
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    • 2023
  • Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.

Structure-activity Relationships of 4-Senecioyloxymethyl-6,7-dimethoxycoumarin Analogues as Anti-Allergic Agents

  • Jeong, Hye-Gwang;Lee, Jee-Hyun;Jung, Sang-Hun;Han, Eun-Hee;Kim, Joo-Hwan;Kim, Dong-Hee;Jin, Mi-Rim;Siripuram, Praveen Kumar;Choi, Yong-Seok;Song, Gyu-Yong
    • Bulletin of the Korean Chemical Society
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    • v.28 no.10
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    • pp.1725-1728
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    • 2007
  • Mast cells are key effector cells in the early phase allergic inflammation and in diverse immunological and pathological processes. In order to understand the effect on reduction of the anti-dinitrophenyl (DNP) IgE antibody-induced β-hexosaminidase release in RBL-2H3 rat mast cells, a novel series of 4-senecioyloxymethyl- 6,7-dimethoxycoumarins (SMDC) was prepared by reacting 4-chloromethyl-6,7-dimethoxycoumarin with various carboxylic acids. Compounds 8-11 with cyclic moiety such as phenyl, thiophenyl, pyridinyl, and furanyl group were found to inhibit-hexosaminidase release more potently (5.98-9.62 μM) than compounds 3- 7 and 12 with acyclic moiety (19.32-76.78 μM). Furthermore, compounds 8 and 9 inhibited IgE-induced ear swelling and significantly reduced systemic passive cutaneous anaphylaxis reaction in mice.

Detection of Edwardsiella tarda, the Pathogenic Bacteria in Freshwater Fishes by Means of the Indirect Fluorescent Antibody Technique (간접형광항체법을 이용한 담수양식어의 병원균 Edwardsiella tarda의 검출)

  • 류해진;조우영;이청산;허강준
    • Korean Journal of Veterinary Service
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    • v.16 no.2
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    • pp.111-119
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    • 1993
  • In this study, we carried out the rapid diagnostic system based on indirect fluorescent anti-body technique (IFAT) for detection of bacterial diseases in cultured freshwater fishes. 1. When the fishes were tested with graded dilution of Edwardsiella tarda FPC 470 bacteria detection from ten fishes Injected with $4.1{\times}10^3$colony forming unit(CFU) /ml, all of them were detected by IFAT but only two fishes were recognizable by the culture method in the tested fishes injected with $4.1{\times}10^3$CFU /ml. 2. The bacteria E. tarda could be detected by IFAT method from 1 to 48hrs after Injection in the tissues tested such as kidney, liver and spleen of the fishes, whereas detection by culture method could be recognized from 1 to 48hrs after injection In the kidney and spleen but it was not possible from preinjection to 1 hr in the liver. 3. Thus, IFAT proved to be more useful technique than plate culture method in the diagnosis of Edwardsiellosis in the freshwater fishes.

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Production of a Monoclonal Antibody to Human $\alpha$-Fetopotein and Development of Monoclonal Antibody-Based Enzyme-Linked Immunosorbent Assays for Human $\alpha$-Fetoprotein (인간 $\alpha$-fetoprotein에 대한 모노클로날 항체의 제조 및 모노클로날 항체를 이용한 효소면역분석법의 개발)

  • Michung Yoon;Hyun-Hee Lee;Youngwon Lee
    • Biomedical Science Letters
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    • v.5 no.1
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    • pp.1-10
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    • 1999
  • This study was attempted to generate a monoclonal antibody against human $\alpha$-fetoprotein (AFP) and to produce an immunoassay, recognizing AFP in plasma and amniotic fluid. AFP was purified from human amniotic fluid and used to immunize mice. Spleens were taken from the mice and the cells were fused with mouse myeloma cells (Sp2/0-Ag-14) for the production of monoclonal antibodies by employing the hybridoma technology. As a result, a hybridoma cell line producing anti-AFP monoclonal antibody was cloned out and designated as MabF22. From isotyping analysis, it was found that monoclonal antibody MabF22 was IgG type with IgG1 heavy chain and k light chain. The binding specificity of MabF22 was analyzed by immunoblotting as well as by ELISA. MabF22 was highly specific, reacting with only AFP-containing samples. The binding affinity was determined by ELISA (free-capture mode) and Scatchard analysis. As a result, the value of Kd was 0.8$\times$10$^{-10}$M. The validity of the MabF22 for AFP assay was examined by two kinds of ELISAs, i.e., non-competitive and competitive ELISA. Both assays revealed that MabF22 reacted well with AFP in sample in a concentration-dependent manner. Standard curve and antibody titration curve were obtained by using purified AFP and MabF22. These results indicate that the monoclonal antibody produced in this study would be useful not only for research purposes but also for further development of immune-diagnostic kit for the measurement of AEP concentration.

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Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

  • In-Ho Kim
    • Journal of Gastric Cancer
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    • v.24 no.1
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    • pp.29-56
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    • 2024
  • In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.