• Title/Summary/Keyword: therapeutic antibody

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The production and application of therapeutic 67Cu radioisotope in nuclear medicine

  • Kim, Gye-Hong;Lee, Kyo Chul;Park, Ji-Ae;An, Gwang-Il;Lim, Sang Mo;Kim, Jung Young;Kim, Byung Il
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.1 no.1
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    • pp.23-30
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    • 2015
  • Radioisotopes emitting low-range highly ionizing radiation such as ${\beta}$-particles are of increasing significance in internal radiotherapy. Among the ${\beta}$-particle emitting radioisotopes, $^{67}Cu$ is an attractive radioisotope for various nuclear medicine applications due to its medium energy ${\beta}$-particle, gamma emissions, and 61.83-hour half-life, which can also be used with $^{64}Cu$ for PET imaging. The production and application of the ${\beta}$-emitting radioisotope $^{67}Cu$ for therapeutic radiopharmaceutical are outlined, and different production routes are discussed. A survey of copper chelators used for antibody labeling is provided. It has been produced via proton, alpha, neutron, and gamma irradiations followed by solvent extraction, ion exchange, electrodeposition. Clinical studies using $^{67}Cu$-labelled antibodies in lymphoma, colon carcinoma and bladder cancer patients are reviewed. Widespread use of this isotope for clinical studies and preliminary treatments has been limited by unreliable supplies, cost, and difficulty in obtaining therapeutic quantities.

Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target

  • Jaewoo Hong;Hyunjhung Jhun;Yeo-Ok Choi;Afeisha S. Taitt;Suyoung Bae;Youngmin Lee;Chang-seon Song;Su Cheong Yeom;Soohyun Kim
    • IMMUNE NETWORK
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    • v.21 no.1
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    • pp.8.1-8.17
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    • 2021
  • The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data

  • Darae Kim;Jin-Oh Choi;Yang Hyun Cho;Kiick Sung;Jaewon Oh;Hyun Jai Cho;Sung-Ho Jung;Hae-Young Lee;Jin Joo Park;Dong-Ju Choi;Seok-Min Kang;Myoung Soo Kim;Jae-Joong Kim
    • Korean Circulation Journal
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    • v.54 no.6
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    • pp.325-335
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    • 2024
  • Background and Objectives: The number of sensitized heart failure patients on waiting lists for heart transplantation (HTx) is increasing. Using the Korean Organ Transplantation Registry (KOTRY), a nationwide multicenter database, we investigated the prevalence and clinical impact of calculated panel-reactive antibody (cPRA) in patients undergoing HTx. Methods: We retrospectively reviewed 813 patients who underwent HTx between 2014 and 2021. Patients were grouped according to peak PRA level as group A: patients with cPRA ≤10% (n= 492); group B: patients with cPRA >10%, <50% (n=160); group C patients with cPRA ≥50% (n=161). Post-HTx outcomes were freedom from antibody-mediated rejection (AMR), acute cellular rejection, coronary allograft vasculopathy, and all-cause mortality. Results: The median follow-up duration was 44 (19-72) months. Female sex, re-transplantation, and pre-HTx renal replacement therapy were independently associated with an increased risk of sensitization (cPRA ≥50%). Group C patients were more likely to have longer hospital stays and to use anti-thymocyte globulin as an induction agent compared to groups A and B. Significantly more patients in group C had positive flow cytometric crossmatch and had a higher incidence of preformed donor-specific antibody (DSA) compared to groups A and B. During follow-up, group C had a significantly higher rate of AMR, but the overall survival rate was comparable to that of groups A and B. In a subgroup analysis of group C, post-transplant survival was comparable despite higher preformed DSA in a desensitized group compared to the non-desensitized group. Conclusions: Patients with cPRA ≥50% had significantly higher incidence of preformed DSA and lower freedom from AMR, but post-HTx survival rates were similar to those with cPRA <50%. Our findings suggest that sensitized patients can attain comparable post-transplant survival to non-sensitized patients when treated with optimal desensitization treatment and therapeutic intervention.

A Study on the Side Effect of Crude Drugs (상용 한약재의 부작용에 관한 연구)

  • Ahn, Dug-Kyun;Kim, Chan-Soo
    • Korean Journal of Pharmacognosy
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    • v.14 no.3
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    • pp.102-106
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    • 1983
  • As many crude drugs are used in the oriental medical field problems on the side effects of these drugs come to the front. To conduct delayed-type hypersensitivity we selected 29 kinds of drugs used frequently for therapeutic agents in oriental medical hospitals (Table I). The cell-mediated immune response was evaluated by measuring the foot pad swelling reaction and humoral immune response by measuring the antibody formation to these crude drugs. Mice were given these drugs intraperioneally for sensitization and challenged with same drug as used for sensitization respectively by intral dermal injection on the left and righ hind foot pad 4 days after senstization and then the foot pads were measured with the dial micrometer. The results were as follow; 1) Gentianae Scabrae Radix, Arecae Semen, Corydalis Tuber, and Paeoniae Radix were significant as delayed-type hypersensitivity inducers. 2) None of the crude drugs tested had effect on the induction of humoral immune response.

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Regulatory T Cells in B Cell Follicles

  • Chang, Jae-Hoon;Chung, Yeonseok
    • IMMUNE NETWORK
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    • v.14 no.5
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    • pp.227-236
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    • 2014
  • Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation $(CD)8^+$ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.

Biological Therapy for Inflammatory Bowel Disease in Children

  • Na, So-Young;Shim, Jung-Ok
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.15 no.1
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    • pp.13-18
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    • 2012
  • The pathogenesis of inflammatory bowel diseases is not very well understood; it is currently thought to be caused by the interaction between genetic factors, environmental factors, intestinal microbes, and immune factors. Biological agents such as anti-tumor necrosis factor (anti-TNF) are widely being used as therapeutic agents. Infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, has been demonstrated to have an effect in the induction and maintenance of remission in Crohn's disease in children. The effects of biological agents, typified by anti-TNFs, in inflammatory bowel disease in children; the recent concern on the administration of biological agents in combination with immunomodulators; and 'Top-down' therapy are some of the topics covered in this review.

Pediatric heart transplantation: how to manage problems affecting long-term outcomes?

  • Kim, Young Hwue
    • Clinical and Experimental Pediatrics
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    • v.64 no.2
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    • pp.49-59
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    • 2021
  • Since the initial International Society of Heart Lung Transplantation registry was published in 1982, the number of pediatric heart transplantations has increased markedly, reaching a steady state of 500-550 transplantation annually and occupying up to 10% of total heart transplantations. Heart transplantation is considered an established therapeutic option for patients with end-stage heart disease. The long-term outcomes of pediatric heart transplantations were comparable to those of adults. Issues affecting long-term outcomes include acute cellular rejection, antibody-mediated rejection, cardiac allograft vasculopathy, infection, prolonged renal dysfunction, and malignancies such as posttransplant lymphoproliferative disorder. This article focuses on medical issues before pediatric heart transplantation, according to the Korean Network of Organ Sharing registry and as well as major problems such as graft rejection and cardiac allograft vasculopathy. To reduce graft failure rate and improve long-term outcomes, meticulous monitoring for rejection and medication compliance are also important, especially in adolescents.

Interstitial Lung Disease and Diffuse Alveolar Hemorrhage, the Two Key Pulmonary Manifestations in Microscopic Polyangiitis

  • Kim, Min Jung;Shin, Kichul
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.4
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    • pp.255-262
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    • 2021
  • Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing vasculitis, which mainly affects small vessels in various organs, especially the lungs. The two key pulmonary manifestations, interstitial lung disease (ILD) and diffuse alveolar hemorrhage (DAH), increase the morbidity and death rate of patients with MPA. ILD is more common in MPA than in other ANCA-associated vasculitis subsets and is primarily associated with myeloperoxidase-ANCA. Unlike alveolar hemorrhage due to pulmonary capillaritis, ILD can initially manifest as isolated pulmonary fibrosis. Of note, its most frequent radiographic pattern is the usual interstitial pneumonia pattern, similar to the characteristic pattern seen in idiopathic pulmonary fibrosis. In this review we present the pathogenesis, clinical manifestations, and radiographic and histopathologic features of ILD and DAH in MPA. We also briefly summarize the outcome and therapeutic options for the two conditions.

Follicular Helper T (Tfh) Cells in Autoimmune Diseases and Allograft Rejection

  • Yun-Hui Jeon;Youn Soo Choi
    • IMMUNE NETWORK
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    • v.16 no.4
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    • pp.219-232
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    • 2016
  • Production of high affinity antibodies for antigens is a critical component for the immune system to fight off infectious pathogens. However, it could be detrimental to our body when the antigens that B cells recognize are of self-origin. Follicular helper T, or Tfh, cells are required for the generation of germinal center reactions, where high affinity antibody-producing B cells and memory B cells predominantly develop. As such, Tfh cells are considered as targets to prevent B cells from producing high affinity antibodies against self-antigens, when high affinity autoantibodies are responsible for immunopathologies in autoimmune disorders. This review article provides an overview of current understanding of Tfh cells and discusses it in the context of animal models of autoimmune diseases and allograft rejections for generation of novel therapeutic interventions.

Efficient Anti-Tumor Immunotherapy Using Tumor Epitope-Coated Biodegradable Nanoparticles Combined With Polyinosinic-Polycytidylic Acid and an Anti-PD1 Monoclonal Antibody

  • Sang-Hyun Kim;Ji-Hyun Park;Sun-Jae Lee;Hee-Sung Lee;Jae-Kyung Jung;Young-Ran Lee;Hyun-Il Cho;Jeong-Ki Kim;Kyungjae Kim;Chan-Su Park;Chong-Kil Lee
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.42.1-42.20
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    • 2022
  • Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2Kb mAbs, and then attached to H-2Kb molecules isolated from the tumor mass (H-2b). Native peptides associated with the H-2Kb molecules of H-2Kb-attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC. Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb. Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.