• Title/Summary/Keyword: Antibody-based therapy

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Human Activated Lymphocyte Treated with Anti-CD3, CD16, CD56 Monoclonal Antibody and IL-2 (Anti-CD3, CD16과 CD56 단일항체와 IL-2를 사용하여 활성화시킨 사람의 림프구)

  • Hong, Seon-Min;Lee, Dong-Wook;Kang, Jin-Gu;Kim, Han-Soo;Cho, Sung-Hoon
    • IMMUNE NETWORK
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    • v.5 no.1
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    • pp.11-15
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    • 2005
  • Background: Throughtout the last three decades, the therapy of leukemias and lymphoma has set the stage for curative cancer therapy in systemic malignant disease. This was the result of an integrated work of basic reaserch and clinical investigators leading to more aggressive albeit tolerable protocol of chemotherapy and radiotherapy. High dose therapy marks the most elaborated strategies in this field today. However, intensification of conventional therapeutic modalities as mentioned has to be based on new approaches and the exploration of new antineoplastic mechanisms. This insight has resulted in immune therapy of cancer. Among the cells of the immune system, natural killer (NK) cells and T cells are of major interest for the development of therapeutic strategies. Methods: Cytotoxicity to target cells was measured by LDH release method, Characterization of activated lymphocyte was measured by Flow cytometry analysis. Anti-CD3, 16, 56 monoclonal antibody and IL-2 were used for the activation of NK and T cell. The analysis of effect of activated lymphocyte, in vivo, were used by Balb/c nude mouse. Results and Conclusion: Cytotoxicity to K562 cells was significantly higher in the mixture group of NK and T cells than that of a group of activating T cells. The survivors and the rate of reduction of size of tumor craft of nude mouse group treatment with activated lymphocyte was higher than that of the group without treatment with activated lymphocyte. Therefore, this results are suggested that the activated lymphocytes by anti-CD3, CD16 and CD56 can reduce the malignancy effect of lymphoma.

COVID-19 Drug Development

  • Kim, Seungtaek
    • Journal of Microbiology and Biotechnology
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    • v.32 no.1
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    • pp.1-5
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    • 2022
  • Diagnostics, vaccines, and drugs are indispensable tools and control measures employed to overcome infectious diseases such as coronavirus disease 2019 (COVID-19). Diagnostic tools based on RT-PCR were developed early in the COVID-19 pandemic and were urgently required for quarantine (testing, tracing and isolation). Vaccines such as mRNA vaccines and virus-vectored vaccines were also successfully developed using new platform technologies within one year after identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the causative agent of COVID-19. Drug development has been conducted in various ways including drug repurposing, convalescent plasma therapy, and monoclonal antibody development. Among the above efforts, this review examines COVID-19 drug development along with the related and upcoming challenges.

Two pediatric cases with hematuria, normal renal function and positive antineutrophil cytoplasmic antibodies

  • Ji Hyeon Lim;Ji Won Jung;Heoun Jeong Go;Joo Hoon Lee;Young Seo Park
    • Childhood Kidney Diseases
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    • v.26 no.2
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    • pp.86-90
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    • 2022
  • Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis requires prompt diagnosis and treatment, since renal function at the time of diagnosis is significantly associated with renal outcomes. Here, we report two pediatric patients with ANCA-positive glomerulonephritis initially presenting with hematuria, mild proteinuria, and normal renal function. The first patient with a high myeloperoxidase-ANCA titer (>134 IU/mL) was diagnosed with rapidly progressive glomerulonephritis based on renal biopsy and treated with immunosuppressive therapy after 10 months of follow-up. The second patient with a low myeloperoxidase-ANCA titer (11 IU/mL) maintained normal kidney function without medication. Two cases showed different clinical course according to ANCA titer.

Quantitation of Antigen-Antibody Reaction Condition for Development of Fluorescence Image-based CD4 Rapid Test (형광 영상 기반 CD4 신속 검사법 개발을 위한 항원-항체 반응 조건 정량화)

  • Kim, Subin;Kim, Jung Kyung
    • Journal of the Korean Society of Visualization
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    • v.13 no.1
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    • pp.35-42
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    • 2015
  • CD4+ T-cell count determines the effectiveness for antiretroviral therapy (ART) in patients with human immunodeficiency virus (HIV). Although ART slows the progression of HIV to AIDS, rapid counting of CD4+ T lymphocytes with a drop of patient's blood sample is urgently needed to ensure timely ART treatment in rural areas. Recently point-of-care CD4 testing devices have been developed by using non-flow based imaging cytometer incorporated with a sample cartridge where CD4+ T cells are reacted with fluorescently tagged specific antibodies. Here we conducted an experimental study using a conventional fluorescence microscope-based imaging system to quantitate the interaction of CD4 antibodies with CD4+ T cells at different reaction conditions. We demonstrated that a fast and affordable point-of-care CD4 test is feasible with a far less amount of antibodies and a shorter incubation time compared with a conventional sample preparation protocol for flow cytometry. We also proposed a general method to evaluate and compare the detection limit across different CD4 counting platforms by using fluorescently labelled microbeads for intensity calibration.

SARS-CoV-2 Antibody Neutralization Assay Platforms Based on Epitopes Sources: Live Virus, Pseudovirus, and Recombinant S Glycoprotein RBD

  • Endah Puji Septisetyani;Pekik Wiji Prasetyaningrum;Khairul Anam;Adi Santoso
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.39.1-39.18
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    • 2021
  • The high virulent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that emerged in China at the end of 2019 has generated novel coronavirus disease, coronavirus disease 2019 (COVID-19), causing a pandemic worldwide. Every country has made great efforts to struggle against SARS-CoV-2 infection, including massive vaccination, immunological patients' surveillance, and the utilization of convalescence plasma for COVID-19 therapy. These efforts are associated with the attempts to increase the titers of SARS-CoV-2 neutralizing Abs (nAbs) generated either after infection or vaccination that represent the body's immune status. As there is no standard therapy for COVID-19 yet, virus eradication will mainly depend on these nAbs contents in the body. Therefore, serological nAbs neutralization assays become a requirement for researchers and clinicians to measure nAbs titers. Different platforms have been developed to evaluate nAbs titers utilizing various epitopes sources, including neutralization assays based on the live virus, pseudovirus, and neutralization assays utilizing recombinant SARS-CoV-2 S glycoprotein receptor binding site, receptor-binding domain. As a standard neutralization assay, the plaque reduction neutralization test (PRNT) requires isolation and propagation of live pathogenic SARS-CoV-2 virus conducted in a BSL-3 containment. Hence, other surrogate neutralization assays relevant to the PRNT play important alternatives that offer better safety besides facilitating high throughput analyses. This review discusses the current neutralization assay platforms used to evaluate nAbs, their techniques, advantages, and limitations.

Preparation and Bioevaluation of 177Lu-labelled Anti-CD44 for Radioimmunotherapy of Colon Cancer

  • Lee, SoYoung;Hong, YoungDon;Jung, SungHee;Choi, SunJu
    • Journal of Radiation Industry
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    • v.9 no.4
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    • pp.187-192
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    • 2015
  • CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the $^{177}Lu$-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based DTPA-NCS and radioimmunoconjugated with $^{177}Lu$ at room temperature within 15 minutes. The stability was tested in human serum. An in vitro study was carried out in HT-29 human colon cancer cell lines. For the biodistribution study $^{177}Lu$-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteine-based DTPA-NCS and purified by a centricon filter system having a molecular cut-off of 50 kDa. Radioimmunoconjugation with $^{177}Lu$ was reacted for 15 min at room temperature. The radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. The anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with $^{177}Lu$. The in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. This radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

C-ANCA-positive glomerulonephritis associated with subacute infective endocarditis caused by Bartonella infection

  • Kim, Min Jeong;Jang, Ha Nee;Lee, Tae Won;Cho, Hyun Seop;Chang, Se-Ho;Kim, Hyun-Jung
    • Journal of Yeungnam Medical Science
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    • v.34 no.1
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    • pp.140-145
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    • 2017
  • Glomerulonephritis (GN) is sometimes associated with infective endocarditis (IE). Bartonella endocarditis is difficult to diagnose because it is rare and cannot be detected by blood culture. This is the first report of cytoplasmic anti-neutrophil cytoplasmic antibody-positive subacute endocarditis-associated GN caused by Bartonella infection in South Korea. A 67-year-old man was hospitalized due to azotemia. He complained of weight loss and anorexia for 6 months. A diagnosis of IE was made based upon echocardiographic detection of vegetations on the mitral and aortic valves and a Bartonella antibody titer of 1:2,048. Renal histology identified focal crescentic GN. Azotemia and proteinuria improved after doxycycline and rifampin treatment combining with steroid therapy.

Radioimmunotherapy in Head and Neck Cancer (두경부암에서 방사면역치료의 역할)

  • Choi, Ik Joon
    • 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.

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

  • Kang, Eun-Ah;Yun, Chae-Ok
    • BMB Reports
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    • v.43 no.12
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    • pp.781-788
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    • 2010
  • An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.

Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors

  • Masaya Igase;Sakuya Inanaga;Shoma Nishibori;Kazuhito Itamoto;Hiroshi Sunahara;Yuki Nemoto;Kenji Tani;Hiro Horikirizono;Munekazu Nakaichi;Kenji Baba;Satoshi Kambayashi;Masaru Okuda;Yusuke Sakai;Masashi Sakurai;Masahiro Kato;Toshihiro Tsukui;Takuya Mizuno
    • Journal of Veterinary Science
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    • v.25 no.1
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    • pp.15.1-15.15
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    • 2024
  • Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.