• Title/Summary/Keyword: Antibody therapy

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Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics

  • Kim, Eunhee G.;Kim, Kristine M.
    • Biomolecules & Therapeutics
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    • v.23 no.6
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    • pp.493-509
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    • 2015
  • Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris$^{(R)}$(anti-CD30-drug conjugate) and Kadcyla$^{(R)}$(anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.

Two cases of antibiotic therapy in dog infected with Brucella canis (Brucella canis 감염견에 대한 항균제 치료)

  • Kim Seong-Guk;Kim Yeong-Hwan;Park In-Hwa;Jang Seong-Jun;Jo Gwang-Hyun;Lee Yang-Soo
    • Korean Journal of Veterinary Service
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    • v.29 no.1
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    • pp.47-53
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    • 2006
  • For examination of antibiotic therapeutic efficacy in canine brucellosis, this examination was carried out two female bitches infected with Brucella canis in Gyeongbuk province, and used combicillin, baytril and doxycycline in susceptible antibiotics at B canis. During 18 month after the termination of antibiotic therapy, blood sample of the two bitches were examined for B canis antibody and antigen. The antibody of one bitch was disappeared at 5 month after antibiotic therapy and the other was continued at 18 month, but two bitches were not detected antigen by blood culture and PCR. Examination of blood chemical value (AST, ALT, urea, creatinine) of two bitches was increased in AST value during antibiotic therapy.

Development of Rapid Antibody-based Therapeutic Platform Correspondence for New Viruses Using Antigen-specific Single Cell Memory B Cell Sorting Technology (항원 특이적 단일 기억 B 세포 분리를 이용한 신종 바이러스 대응 신속 항체 플랫폼 개발)

  • Jiyoon Seok;Suhan Jung;Ye Gi Han;Arum Park;Jung Eun Kim;Young Jo Song;Chi Ho Yu;Hyeongseok Yun;Se Hun Gu;Seung-Ho Lee;Yong Han Lee;Gyeunghaeng Hur;Woong Choi
    • 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.

B3(Fab)-streptavidin Tetramer Has Higher Binding Avidity than B3(scFv)-streptavidin Tetramer

  • Won, Jae-Seon;Kang, Hye-Won;Nam, Pil-Won;Choe, Mu-Hyeon
    • 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.

Immunogenicity of the ChAdOx1 nCoV-19 vaccine in patients with hematologic malignancies

  • Chayapa Thookhamme;Manassamon Navinpipat;Aimwipa Sasakul;Pakthipa Pattarakosol;Kamoltip Lertchaisataporn;Kriangkrai Tawinprai;Pannee Praditsuktavorn
    • Clinical and Experimental Vaccine Research
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    • v.12 no.2
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    • pp.107-115
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    • 2023
  • Purpose: The present study aimed to study the immunogenicity of the ChAdOx1 nCoV-19 vaccine in patients with hematologic malignancies. Materials and Methods: This prospective cohort study of hematology patients aimed to evaluate their antibody levels against the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and seroconversion rates following two doses of the ChAdOx1 nCoV-19 vaccine. Between June and July 2021, we enrolled 61 patients and included 44 patients in our analysis. Antibody levels were assessed 8 and 4 weeks after the first and second injections, respectively, and compared with those of a healthy group. Results: Eight weeks after the first dose, the geometric mean antibody level was 1.02 binding antibody units (BAU)/mL in the patient group and 37.91 BAU/mL in the healthy volunteer group (p<0.01). Four weeks after the second dose, the geometric mean antibody level was 9.44 BAU/mL in patients and 641.6 BAU/mL in healthy volunteers (p<0.01). The seroconversion rates 8 weeks after the first dose were 27.27% and 98.86% in the patient and healthy volunteer groups, respectively (p<0.001). The seroconversion rate 4 weeks after the second dose was 47.73% in patients and 100% in healthy volunteers. Factors leading to lower seroconversion rates were rituximab therapy (p=0.002), steroid therapy (p<0.001), and ongoing chemotherapy (p=0.048). Factors that decreased antibody levels were hematologic cancer (p<0.001), ongoing chemotherapy (p=0.004), rituximab (p<0.001), steroid use (p<0.001), and absolute lymphocyte count <1,000/mm3 (p=0.009). Conclusion: Immune responses were impaired in individuals with hematologic malignancies, particularly patients undergoing ongoing therapy and B-cell-depleting therapy. Additional vaccinations should be considered for these patients, and further investigated.

Specific Targeting of Fluorescein Isothiocyanate with Ep-CAM Antibody(Specific targeting of FITC with Ep-CAM Antibody)

  • Lee, Young-Tae;Tae, Gun-Sik
    • Journal of Photoscience
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    • v.10 no.3
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    • pp.237-240
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    • 2003
  • The tetradecameric peptide (K47-K60) near the NH$_2$-terminal region of epithelial-cell adhesion molecule (Ep-CAM) was chosen as antigenic site and a polyclonal antibody was generated, which could recognize Ep-CAM from the mouse colon tissue or the colon cancer cell, CT-26, in Western blot analysis. Then, the fluorescein isothiocyanate (FITC), a fluorescence dye, was conjugated with the affinity purified Ep-CAM antibody using thiocyanate and the amino groups of FITC and antibody, respectively. The molar ratio of FITC to antibody was estimated approximately 1.86 to 1.00 by measuring the optical densities at 492 nm and 280 nm. Ep-CAM antibody-FITC conjugate was then used for immunohistochemistry of the CT-26 cells. Judging from the shapes formed by fluorescence, the Ep-CAM antibody could delivered FITC to the surface of cells in which Ep-CAM was expressed. This result implies that Ep-CAM antibody could be also used for the tissue-specific delivery of the photosensitizer to the target protein via antigen-antibody interaction.

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Antibody Engineering

  • Hong, Hyo-Jeong;Kim, Sun-Taek
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.7 no.3
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    • pp.150-154
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    • 2002
  • Monoclonal antibodies (Mabs) have been used as diagnostic and analytical reagents since hybridoma technology was invented in 1975. In recent years, antibodies have become increasingly accepted as therapeutics for human diseases, particularly for cancer, viral infection and autoimmune disorders. An indication of the emerging significance of antibody-based therapeutics is that over a third of the proteins currently undergoing clinical trials in the United States are antibodies. Until the late 1980's, antibody technology relied primarily on animal immunization and the expression of engineered antibodies. However, the development of methods for the expression of antibody fragments in bacteria and powerful techniques for screening combinatorial libraries, together with the accumulating structure-function data base of antibodies, have opened unlimited opportunities for the engineering of antibodies with tailor-made properties for specific applications. Antibodies of low immunogenicity, suitable for human therapy and in vivo diagnosis, can now be developed with relative ease. Here, antibody structure-function and antibody engineering technologies are described.

Cell-Specific Targeting of Texas Red with Anti-Ep-CAM Antibody

  • Lee, Soo-Chul;Tae, Gun-Sik
    • Journal of Photoscience
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    • v.12 no.3
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    • pp.123-127
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    • 2005
  • The polyclonal antibody was generated against the peptide fragment of 62 amino acid residues (D 181-T242) near the COOH-terminal region of the extracellular domain of epithelial-cell adhesion molecule (Ep-CAM) and shown to be able to recognize Ep-CAM in competitive ELISA. Then, sulforhodamine 101 acid chloride (so called Texas red), a fluorescence dye, was conjugated to the affinity-purified anti-Ep-CAM antibody utilizing the reaction between the aliphatic amines of antibody and the sulfonyl chloride of Texas red. The molar ratio of Texas red to antibody was estimated to be approximately 1.86 by measuring optical densities at 280 nm and 596 nm, implying that the two molecules of Texas red at most were conjugated to antibody. The anti-Ep-CAM antibody-Texas red conjugate was then used for immunohistochemistry of CT-26 murine colon carcinoma cells. Based upon the fluorescence microscope images, anti-Ep-CAM antibody is able to deliver Texas red specifically to the surface of CT-26 cells on which Ep-CAM was actively expressed. This result indicates that anti-Ep-CAM antibody could be useful for the tissue-specific delivery of photosensitizers via antigen-antibody interaction.

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Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy

  • Cho, Jaewon;Tae, Nara;Ahn, Jae-Hee;Chang, Sun-Young;Ko, Hyun-Jeong;Kim, Dae Hee
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.418-426
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    • 2022
  • Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1+ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8+ T cells having CD8+CD44+CD62Llow phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

The Principles and Practices of Immunocytochemical method in Light Microscopic Level (광학 현미경적 수준에서의 면역조직화학적 방법의 원리 및 실제)

  • Kim Jin-Sang
    • The Journal of Korean Physical Therapy
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    • v.3 no.1
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    • pp.229-250
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    • 1991
  • The study was carried out to investigate and review the principles and practices of immunocytochemical method in light microscopic level. The results were as follows. 1. Immunocytochemistry is the method to search out the intracellular position of the specific meterials using antigen -antibody reaction. 2. The chief items in immunocytochemistry are antigen, antibody and chromogen. 3. The identifical fixation is cardiac perfusion fixation. 4. The tissue slides must be prepared by vibratomy. 5. All stainings are carried out with free floating staining method. 6. There are polyclonal and monoclonal antibodies used in immunocytochemistry.

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