• Journal of Ginseng Research
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• v.48 no.2
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• pp.190-201
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• 2024

Background: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results: CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.

• Journal of the Korea Institute of Military Science and Technology
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• v.27 no.1
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• pp.116-125
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• 2024

The COVID-19 pandemic is not over despite the emergency use authorization as can see recent COVID-19 daily confirmed cases. The viruses are not only difficult to diagnose and treat due to random mutations, but also pose threat human being because they have the potential to be exploited as biochemical weapons by genetic manipulation. Therefore, it is inevitable to the rapid antibody-based therapeutic platform to quickly respond to future pandemics by new/re-emerging viruses. Although numerous researches have been conducted for the fast development of antibody-based therapeutics, it is sometimes hard to respond rapidly to new viruses because of complicated expression or purification processes for antibody production. In this study, a novel rapid antibody-based therapeutic platform using single B cell sorting method and mRNA-antibody. High immunogenicity was caused to produce antibodies in vivo through mRNA-antigen inoculation. Subsequently, antigen-specific antibody candidates were selected and obtained using isolation of B cells containing antibody at the single cell level. Using the antibody-based therapeutic platform system in this study, it was confirmed that novel antigen-specific antibodies could be obtained in about 40 days, and suggested that the possibility of rapid response to new variant viruses.

• Korean Journal of Clinical Pharmacy
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• v.22 no.1
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• pp.21-29
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• 2012

Modern biologics are biotechnology-derived therapeutics, including recombinant therapeutic proteins like monoclonal antibodies, cytokines and tissue growth factors. Although the pharmacokinetics of therapeutic biologics should be evaluated based on the same general principles as small molecules, careful considerations should be given to bioanalytics and pharmacokinetics when designing pharmacokinetic studies of biologics during their drug development, due to their different physicochemical properties compared with small molecules. The aim of this study was to develop a draft guidance on pharmacokinetic studies of therapeutic biologics in clinical studies. All the elements outlined in the current Food and Drug Administration (FDA), European Medicinal Agency (EMEA), and International Conference on Harmonisation (ICH) guidelines and regulations, and the related literatures previously published were searched and evaluated. In this draft guidance, the specific problems related to the pharmacokinetics of therapeutic biologics that need special consideration during drug development process were addressed, and differences in pharmacokinetic characteristics between biologics and small molecules affecting the content of the development programme were presented.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.185-191
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• 2008

While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (lressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.905-910
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• 2016

Breast cancer is one of the major threats to female health, and its incidence is rapidly increasing in many countries. Currently, breast cancer is treated with surgery, followed by chemotherapy or radiation therapy, or both. However, a substantial proportion of breast cancer patients might have a risk for local relapse that leads to recurrence of their disease and/or metastatic breast cancer. Therefore searching for new and potential strategies for breast cancer treatment remains necessary. Immunotherapy is an attractive and promising approach that can exploit the ability of the immune system to identify and destroy tumors and thus prevent recurrence and metastatic lesions. The most promising and attractive approach of immunotherapeutic research in cancer is the blockade of immune checkpoints. In this review, we discuss the potential of certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint inhibitors may represent future standards of care for breast cancer as monotherapy or combined with standard therapies.

• Proceedings of the Korean Society of Fisheries Technology Conference
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• 2000.05a
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• pp.446-446
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• 2000

Specific polyclonal and/or monoclonal antibodies (MAbs) to immunoglobulins (Igs) and their subunits have proved to be valuable tools in immunological research and in immunological assays. In this study, we developed and characterized MAbs against flounder serum Igs. To obtain the pure flounder serum Igs, mouse IgG (mIgG) was immunized to flounder. Flounder Igs were purified by using mIgG-agarose affinity column chromatography. The structure of purified flounder Ig was observed, on denatured SDS-PAGE, to be composed of two heavy chains (77 and 72 kd) and two light chains (28 and 26 kd). MAbs were produced by fusion of myeloma cells (SP2/0) with Balb/c mouse spleen cells previously primed with the flounder Igs. Finally, three hybridoma clones, FIM 511, FIM 519 and FIM 562 were established to recognize both 2 heavy chains, 26 kd of light chain and 28 kd of light chain, respectively. On the other hand, the flounder immune sera collected on the weekly basis were tested on ELISA and immunoblot analysis whether boosting effect is present in flounder humoral immune system. As a result, the secondary immune response in flounder was ascertained on ELISA, but not on immunoblot analysis. Further, we observed an alteration of serum protein levels following immunization. Our MAbs and basic information on flounder humoral immune system obtained in this study will be helpful to control and monitor the efficiency of fish vaccines and therapeutic process of flounder diseases.

• YAKHAK HOEJI
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• v.53 no.3
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• pp.119-124
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• 2009

Cell-cell adhesion managed by various adhesion molecules plays an important role in regulating functional activation of cells. This event mediates attachment of inflammatory cells to endothelial cells, interaction of antigen-presenting cells with T cells and metastatic adherence of cancer cells to epithelial tissue cells. Therefore, this cellular response is considered as one of therapeutic target to treat various cancers and inflammatory diseases. To develop proper model for evaluation of functional activation of adhesion molecules, the ability of U937 and Jurkat T cells responsive to various adhesion inducers such as phorbal-12-myristate-13-acetate (PMA), staurosporin and monoclonal antibodies to CD29, CD43 and CD98 was investigated using quantitative cell-cell adhesion assay. U937 cells made more cell-cell clusters by the treatment of antibodies to CD29 and CD43 than Jurkat T cells, while Jurkat T cells exhibited increased cell-cell adhesion ability in CD98 antibody treatment. In agreement, the surface levels of CD29 and CD98 were highly observed in U937 and Jurkat T cells, respectively. Therefore, our data suggest that Jurkat T and U937 cells can be used for model system to evaluate functional activation of adhesion molecules such as CD29 and CD98.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1101-1106
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• 2009

Multivalent and multi-specific antibodies can provide valuable tools for bio-medical research, diagnosis and therapy. In antigen-antibody interactions, the avidity of antibodies depends on the affinity and the number of binding sites.$^1$ As artificial multivalent antibody agents, single chain Fv-streptavidin fusion tetramer proteins $(scFv-SA)_4$ have been previously tested.$^{1,\;2}$ Although, the Fab domain is known to be more stable than scFv in animal models,$^{3,\;4}$ it has never been used to make a multivalent agent with a streptavidin fusion. In this study, we prepared tetra-valent $(Fab-cSA)_4$ by fusing Fab with core streptavidin (cSA). This molecule was made using inclusion body production, refolding and chromatography purification. Affinities of the Fab-cSA tetramer and a scFv-cSA tetramer to a cell surface antigen were compared by ELISA using biotin-HRP. The Fab-cSA tetramer showed higher binding avidity than the scFv-cSA tetramer. The higher binding avidity of the Fab-cSA tetramer demonstrates its potential as a therapeutic agent for target-specific antibody therapy.

• Toxicological Research
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• v.12 no.1
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• pp.81-86
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• 1996

Antigenicity of recombinant human interferon $\beta$(LB00013), a newly developed drug for anti-cancer and anti-viral therapeutic use, was investigated in mice and guinea pigs. The following results were obtained: 1. Mice showed no production of antibodies against LB00013 sensitized with aluminum hydroxide gel (Alum) as an adjuvant, when judged by the heterologous passive cutaneous anaphylaxis (PCA) test in rats. Meanwhile, antibodies against ovalbumin (OVA) sensitized with Alum were clearly detected. 2. In guinea pigs, the sensitization of neither LB00013 only nor LB00013 with complete Freund's adjuvant (CFA) produced positive reactions in the homologous active systemic anaphylaxis (ASA) and the PCA tests. Meanwhile, the sensitization of OVA with CFA produced positive reactions in both PCA and ASA. 3. A LB00013-specific reaction was not observed in an indirect hemagglutination(IHA) assay using sera isolated from LB00013 sensitized mice. The present results suggested that LB00013 may have no antigenic potential in mice and guinea pigs.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.12
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• pp.637-643
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• 2018

Radioimmunotherapy (RIT) is a therapy that takes advantage of the "cross-fire" effect of emitted radiation by radionuclides conjugated to tumor-directed monoclonal antibodies (mAb) (including those fragments) or peptides. While RIT has been successfully employed for the treatment of lymphoma, mostly with radiolabeled antibodies against CD20 [$^{90}yttrium$ ($^{90}Y$)-ibritumomab tiuxetan; $Zevalin^{(R)}$ and $^{131}iodine$ ($^{131}I)-tositumomab$; $Bexxar^{(R)}$], its use in solid tumors is more challenging, so far. Immuno-PET, a tool for tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and guide mAb-based therapy. RIT in solid tumors including head and neck cancer may be an alternative treatment with advances in various biological, chemical, and treatment procedures, and it may help to reduce unnecessary exposure and enhance the therapeutic efficacy. Also, immuno-PET based on RIT might play an important role in cancer staging, in patients or targets selection of targeted therapeutics and in monitoring the response of targeted therapeutics as precision medicine. In this review, fundamentals of RIT/immune-PET and current knowledge of the preclinical/clinical trials in RIT for solid tumor including head and neck cancer are reviewed.