scholarly journals Humanized Monoclonal Antibody That Passively Protects Mice against Systemic and Intranasal Ricin Toxin Challenge

2016 ◽  
Vol 23 (9) ◽  
pp. 795-799 ◽  
Author(s):  
Greta Van Slyke ◽  
Erin K. Sully ◽  
Natasha Bohorova ◽  
Ognian Bohorov ◽  
Do Kim ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Lethal Dose ◽  
Murine Monoclonal Antibody ◽  
Serum Concentrations ◽  
Immunodominant Epitope ◽  
Ricin Toxin ◽  
Humanized Monoclonal Antibody

ABSTRACTPB10 is a murine monoclonal antibody against an immunodominant epitope on ricin toxin's enzymatic subunit. Here, we characterize a fully humanized version of PB10 IgG1 (hPB10) and demonstrate that it has potentin vitroandin vivotoxin-neutralizing activities. We also report the minimum serum concentrations of hPB10 required to protect mice against 10 times the 50% lethal dose of ricin when delivered by injection and inhalation.

scholarly journals A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 215 ◽  
Author(s):  
Yinghui Rong ◽  
Michael Pauly ◽  
Adrian Guthals ◽  
Henry Pham ◽  
Dylan Ehrbar ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mouse Model ◽  
Therapeutic Efficacy ◽  
Lethal Dose ◽  
Immunodominant Epitope ◽  
Ricin Toxin ◽  
Humanized Monoclonal Antibody ◽  
Antibody Cocktail ◽  
Binding Subunit

PB10 IgG1, a monoclonal antibody (MAb) directed against an immunodominant epitope on the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice and non-human primates from an aerosolized lethal-dose RT challenge. However, it was recently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when co-administered with a second MAb, SylH3, targeting RT’s binding subunit (RTB). Here we report that the PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP) in a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to engineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly efficacious in the mouse model, thereby opening the door to future testing in non-human primates.

scholarly journals Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4127
Author(s):  
Aline de Cristo Soares Alves ◽  
Franciele Aline Bruinsmann ◽  
Silvia Stanisçuaski Guterres ◽  
Adriana Raffin Pohlmann
Keyword(s):  
Monoclonal Antibody ◽  
Physicochemical Characterization ◽  
Vascular Endothelial ◽  
Organic Nanoparticles ◽  
Humanized Monoclonal Antibody ◽  
Angiogenesis Process ◽  
Endothelial Growth Factor ◽  
Drug Pharmacokinetics

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

scholarly journals A Partially Humanized Monoclonal Antibody to Human IFN-γ Inhibits Cytokine Effects both In Vitro and In Vivo

2002 ◽  
Vol 55 (3) ◽  
pp. 284-292 ◽  
Author(s):  
S. Fiorentini ◽  
G. De Panfilis ◽  
G. Pasolini ◽  
C. Bonfanti ◽  
A. Caruso
Keyword(s):  
Monoclonal Antibody ◽  
Humanized Monoclonal Antibody ◽  
Ifn Γ

An Agonist Murine Monoclonal Antibody to the Human c-Mpl Receptor Stimulates Megakaryocytopoiesis

Blood ◽  
1998 ◽  
Vol 92 (6) ◽  
pp. 1981-1988
Author(s):  
Bijia Deng ◽  
Naheed Banu ◽  
Beth Malloy ◽  
Philip Hass ◽  
Jian Feng Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Murine Monoclonal Antibody ◽  
In Vivo Studies ◽  
Severe Thrombocytopenia ◽  
Colony Forming Unit ◽  
Liquid Culture System ◽  
Primary Bone ◽  
American Society

Thrombopoietin (TPO) is a hematopoietic growth factor that stimulates megakaryocytopoiesis and platelet production in vivo and promotes the development of identifiable megakaryocytes in vitro. We have developed a murine monoclonal antibody, BAH-1, raised against human megakaryocytic cells, which specifically recognizes the c-Mpl receptor and shows agonist activity by stimulating megakaryocytopoiesis in vitro. BAH-1 antibody specifically binds to platelets and to recombinant c-Mpl with high affinity. Similar to TPO, BAH-1 alone supported the formation of colony-forming unit-megakaryocyte (CFU-MK) colonies. The combination of BAH-1 plus interleukin-3 or of BAH-1 plus human TPO significantly increased the number of human CFU-MK colonies. In addition, BAH-1 monoclonal antibody stimulated the proliferation and maturation of primary bone marrow megakaryocytes in a dynamic heterogeneous liquid culture system. Individual large megakaryocytes as well as small megakaryocytic cells were observed in cultures of CD34+ CD41+cells in the presence of BAH-1 antibodies. Similar to TPO, BAH-1 antibody induced a significant response of murine immature megakaryocytes as observed by an increase in the detectable numbers of acetylcholinesterase-positive megakaryocytes. No effects of BAH-1 antibody were observed on colony-forming unit–granulocyte-macrophage, burst-forming unit-erythroid, or colony-forming unit-erythroid colonies. In vivo studies showed that BAH-1, alone or in combination with TPO, expands the numbers of megakaryocytic progenitor cells in myelosuppressed mice. This antibody should prove useful in understanding the structure-function aspects of the c-Mpl receptor as well as in evaluating the effects of the sustained activation of this receptor in preclinical models of severe thrombocytopenia. © 1998 by The American Society of Hematology.

scholarly journals Hemagglutinin stalk-based monoclonal antibody elicits broadly reactivity against group 1 influenza A virus

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jingjin Huang ◽  
Nan Huang ◽  
Menglu Fan ◽  
Lingcai Zhao ◽  
Yan Luo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Broad Spectrum ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Linear Epitope ◽  
Group 1

Abstract Background Influenza virus remains a continuous and severe threat to public health worldwide, and its prevention and treatment have always been a major international issue. Because of its ability to evade immune surveillance through rapid antigenic drift and antigenic shift, broad-spectrum vaccines seem increasingly important. Methods A mAb named 3C12 from an immortalized hybrid cell was generated via immunizing mice with HA2 protein from A/chicken/Anhui/BRI99/2016 (AH/BRI99/16, H9N2) generated by prokaryotic expression. Then, its broad-spectrum activity was analyzed by WB and IFA. Next, the minimal linear epitope was identified via analyzing the reaction of a series of HA truncations with 3C12. Finally, the protective effects of 3C12 were evaluated in vitro and in vivo infection experiments. Results The mAb could react with the viruses of subtypes H1, H2, H5, H8, H9, H12, H13, H16, and HA protein of H18 in group 1, but failed to react with viruses in group 2. The minimal linear epitope targeted by the mAb was 433NAELLVL439 in full length of HA and localized in the C-helix region of HA2 (residue 95-101, HA2 numbering). What’s more, the mAb 3C12 inhibited H1, H2, H5, H8, H9, H12, H13 and H16 virus-replication in vitro and also has shown effectiveness in preventing and treating disease in mice challenged with lethal dose of AH/BRI99/16 (H9N2) virus in vivo. These results suggested that the broadly reactive anti-HA stem mAb 3C12 exhibited prophylactic and therapeutic efficacy. Conclusions Here, we have demonstrated that the linear epitope identified in this study could be a novel target for developing broad-spectrum influenza diagnostics or vaccine design, and the HA2-based monoclonal antibody is indeed a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.

scholarly journals In vitro and In vivo Characterization of 64Cu-Labeled AbegrinTM, a Humanized Monoclonal Antibody against Integrin αvβ3

2006 ◽  
Vol 66 (19) ◽  
pp. 9673-9681 ◽  
Author(s):  
Weibo Cai ◽  
Yun Wu ◽  
Kai Chen ◽  
Qizhen Cao ◽  
David A. Tice ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Integrin Αvβ3 ◽  
Humanized Monoclonal Antibody ◽  
In Vivo Characterization

scholarly journals Hemagglutinin Stalk-based Monoclonal Antibody Elicits Broadly Reactivity Against Group 1 Influenza A Virus

2020 ◽  
Author(s):  
Jingjin Huang ◽  
Nan Huang ◽  
Menglu Fan ◽  
Lingcai Zhao ◽  
Yan Luo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Broad Spectrum ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Linear Epitope ◽  
Group 1

Abstract Background: Influenza virus remains a continuous and serious threat to public health worldwide, and its prevention and treatment have always been a major international issue. Because of its ability to evade immune surveillance through rapid antigenic drift and antigenic shift, broad-spectrum vaccines seem increasingly important. Methods: A mAb named 3C12 from an immortalized hybrid cell was generated via immunizing mice with HA2 protein from A/chicken/Anhui/BRI99/2016 (AH/BRI99/16, H9N2) generated by prokaryotic expression. Then, its broad-spectrum activity was analyzed by WB and IFA. Next, the minimal linear epitope was identified via analyzing the reaction of a series of HA truncations with 3C12. Finally, the protective effects of 3C12 were evaluated in vitro and in vivo infection experiments.Results: The mAb could react with the viruses of subtypes H1, H2, H5, H8, H9, H12, H13, H16, and HA protein of H18 in group 1, but failed to react with viruses in group 2. The minimal linear epitope targeted by the mAb was 433NAELLVL439 in full length of HA and localized in the C-helix region of HA2 (residue 95-101, HA2 numbering). What’s more, the mAb 3C12 inhibited H1, H2, H5, H8, H9, H12, H13 and H16 virus-replication in vitro and also has shown effectiveness in preventing and treating disease in mice challenged with lethal dose of AH/BRI99/16 (H9N2) virus in vivo. These results suggested that the broadly reactive anti-HA stem mAb 3C12 exhibited prophylactic and therapeutic efficacy.Conclusions: Here, we have demonstrated that the linear epitope identified in this study could be a novel target for developing broad-spectrum influenza diagnostics or vaccine design, and the HA2-based monoclonal antibody is indeed a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.

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