scholarly journals A human monoclonal antibody 264RAD targeting αvβ6 integrin reduces tumour growth and metastasis, and modulates key biomarkers in vivo

Oncogene ◽  
2012 ◽  
Vol 32 (37) ◽  
pp. 4406-4416 ◽  
Author(s):  
C Eberlein ◽  
J Kendrew ◽  
K McDaid ◽  
A Alfred ◽  
J S Kang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumour Growth ◽  
Human Monoclonal Antibody ◽  
Αvβ6 Integrin

scholarly journals Evaluation of Fab and F(ab′)2 Fragments and Isotype Variants of a Recombinant Human Monoclonal Antibody against Shiga Toxin 2

2010 ◽  
Vol 78 (3) ◽  
pp. 1376-1382 ◽  
Author(s):  
Donna E. Akiyoshi ◽  
Abhineet S. Sheoran ◽  
Curtis M. Rich ◽  
L. Richard ◽  
Susan Chapman-Bonofiglio ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Shiga Toxin ◽  
Chinese Hamster Ovary Cells ◽  
Human Monoclonal Antibody ◽  
Chinese Hamster ◽  
The Body ◽  
Neutralization Activity ◽  
Shiga Toxin 2

ABSTRACT 5C12 HuMAb is a human monoclonal antibody against the A subunit of Shiga toxin 2 (Stx2). We have previously shown that 5C12 HuMAb effectively neutralizes the cytotoxic effects of this toxin by redirecting its transport within the cell and also by neutralizing the toxin's ability to inhibit protein synthesis. The 5C12 HuMAb and its recombinant IgG1 version protect mice at a dose of 0.6 μg against a lethal challenge of Stx2. The contribution of the Fc region to this observed neutralization activity of the 5C12 antibody against Stx2 was investigated in this study. Using recombinant DNA technology, 5C12 isotype variants (IgG1, IgG2, IgG3, and IgG4) and antibody fragments [Fab, F(ab′)2] were expressed in Chinese hamster ovary cells and evaluated in vitro and in vivo. All four 5C12 isotype variants showed protection in vitro, with the IgG3 and IgG4 variants showing the highest protection in vivo. The Fab and F(ab′)2 fragments also showed protection in vitro but no protection in the mouse toxicity model. Similar results were obtained for a second HuMAb (5H8) against the B subunit of Stx2. The data suggest the importance of the Fc region for neutralization activity, but it is not clear if this is related to the stability of the full-length antibody or if the Fc region is required for effective elimination of the toxin from the body.

In vivo and in vitro studies with a novel human monoclonal antibody against tetanus neurotoxin

Toxicon ◽  
2013 ◽  
Vol 75 ◽  
pp. 216
Author(s):  
E. Girard ◽  
P. Villeneuve ◽  
V. Devos ◽  
A.S. Dezetter ◽  
A. Fontayne ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
In Vitro Studies ◽  
Tetanus Neurotoxin

Supression of FLT3-Expressing Leukemia by a Monoclonal Antibody-Auristatin Conjugate.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1788-1788
Author(s):  
Yiwen Li ◽  
Hongli Li ◽  
Mei-Nai Wang ◽  
Rajiv Bassi ◽  
Dale Ludwig ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Flow Cytometric Analysis ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Lymphoid Leukemia ◽  
Juxtamembrane Region

Abstract The receptor tyrosine kinase FLT3 is overexpressed in blasts of ~90% of acute myelogenous leukemia (AML) and the majority of B-lymphoid leukemia patients. Internal tandem duplications (ITDs) in the juxtamembrane region and point mutations in the kinase domain of FLT3 are found in ~37% of AML patients and are associated with a poor prognosis. We have recently developed a fully human monoclonal antibody (IMC-EB10) which binds with high affinity to FLT3 receptor on human leukemia cells. In the present study, a novel auristatin conjugate of the anti-FLT3 antibody (EB10-MMAF) was prepared using a dipeptide linker that allows for drug release inside the lysosomes of antigen-positive cells. The MMAF conjugates were stable in buffers and plasma. EB10-MMAF (drug/antibody raito = 8) was highly potent, and selectively inhibited the growth of FLT3-expressing leukemia cells with an IC50 of 0.19 nM and 0.08 nM for MV4;11 and BaF3-ITD cells (both positive for FLT3-ITD), 1.11 nM, 6.18 nM and 1.82 nM for REH , EOL-1, EM3 cells (all three positive for wild-type FLT3), and 135 nM for JM1 (negative for FLT3). An MMAF conjugate with a control antibody was not active in these cell lines (IC50s > 5.9 uM). Flow cytometric analysis with annexin V indicated that EB10-MMAF treatment induced apoptosis of leukemia cells in vitro. In vivo treatment with EB10-MMAF strongly inhibited leukemia growth and prolonged survival of mice in both EOL-1 and BaF3-ITD leukemia models. In summary, immunoconjugates composed of a fully human anti-FLT3 antibody and a potent auristatin drug may provide a valuable therapeutic approach for AML and other FLT3-positive leukemias.

scholarly journals Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus

2010 ◽  
Vol 201 (6) ◽  
pp. 946-955 ◽  
Author(s):  
Barry Rockx ◽  
Eric Donaldson ◽  
Matthew Frieman ◽  
Timothy Sheahan ◽  
Davide Corti ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Severe Acute Respiratory Syndrome ◽  
Human Monoclonal Antibody ◽  
Antibody Neutralization

scholarly journals Engineering the surface properties of a human monoclonal antibody prevents self-association and rapid clearance in vivo

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Claire L. Dobson ◽  
Paul W. A. Devine ◽  
Jonathan J. Phillips ◽  
Daniel R. Higazi ◽  
Christopher Lloyd ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Surface Properties ◽  
Human Monoclonal Antibody ◽  
Rapid Clearance ◽  
Self Association

scholarly journals A Human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo

Hepatology ◽  
2011 ◽  
Vol 55 (2) ◽  
pp. 364-372 ◽  
Author(s):  
Philip Meuleman ◽  
Maria Teresa Catanese ◽  
Lieven Verhoye ◽  
Isabelle Desombere ◽  
Ali Farhoudi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Scavenger Receptor ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Viral Spread ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Heterosubtypic Protection Conferred by the Human Monoclonal Antibody PN-SIA28 against Influenza A Virus Lethal Infections in Mice

2015 ◽  
Vol 59 (5) ◽  
pp. 2647-2653 ◽  
Author(s):  
Miguel Retamal ◽  
Yacine Abed ◽  
Chantal Rhéaume ◽  
Francesca Cappelletti ◽  
Nicola Clementi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Body Weight ◽  
Influenza Virus ◽  
Influenza A ◽  
Human Monoclonal Antibody ◽  
Influenza A Viruses ◽  
Virus Challenge ◽  
Influenza A H1n1

ABSTRACTPN-SIA28 is a human monoclonal antibody (Hu-MAb) targeting highly conserved epitopes within the stem portion of the influenza virus hemagglutinin (HA) (N. Clementi, et al, PLoS One 6:e28001, 2011,http://dx.doi.org/10.1371/journal.pone.0028001). Previousin vitrostudies demonstrated PN-SIA28 neutralizing activities against phylogenetically divergent influenza A subtypes. In this study, the protective activity of PN-SIA28 was evaluated in mice inoculated with lethal influenza A/WSN/33 (H1N1), A/Quebec/144147/09 (H1N1)pdm09, and A/Victoria/3/75 (H3N2) viruses. At 24 h postinoculation (p.i.), animals received PN-SIA28 intraperitoneally (1 or 10 mg/kg of body weight) or 10 mg/kg of unrelated Hu-MAb (mock). Body weight loss and mortality rate (MR) were recorded for 14 days postinfection (p.i.). Lung viral titers (LVT) were determined at day 5 p.i. In A/WSN/33 (H1N1)-infected groups, all untreated and mock-receiving mice died, whereas MRs of 87.5% and 25% were observed in mice that received PN-SIA28 1 and 10 mg/kg, respectively. In influenza A(H1N1) pdm09-infected groups, an MR of 75% was recorded for untreated and mock-treated groups, whereas the PN-SIA28 1-mg/kg and 10-mg/kg groups had rates of 62.5% and 0%, respectively. In A/Victoria/3/75 (H3N2)-infected animals, untreated and mock-treated animals had MRs of 37.5% and 25%, respectively, and no mortalities were recorded after PN-SIA28 treatments. Accordingly, PN-SIA28 treatments significantly reduced weight losses and resulted in a ≥1-log reduction in LVT compared to the control in all infection groups. This study confirms that antibodies targeting highly conserved epitopes in the influenza HA stem region, like PN-SIA28, not only neutralize influenza A viruses of clinically relevant subtypesin vitrobut also, more importantly, protect from a lethal influenza virus challengein vivo.

Demonstration of an in vivo generated sub-picomolar affinity fully human monoclonal antibody to interleukin-8

2005 ◽  
Vol 334 (4) ◽  
pp. 1004-1013 ◽  
Author(s):  
Palaniswami Rathanaswami ◽  
Shelly Roalstad ◽  
Lorin Roskos ◽  
Qiaojuan Jane Su ◽  
Steve Lackie ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Interleukin 8

scholarly journals Structures of complexes formed by H5 influenza hemagglutinin with a potent broadly neutralizing human monoclonal antibody

2015 ◽  
Vol 112 (30) ◽  
pp. 9430-9435 ◽  
Author(s):  
Xiaoli Xiong ◽  
Davide Corti ◽  
Junfeng Liu ◽  
Debora Pinna ◽  
Mathilde Foglierini ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Antiviral Agents ◽  
Influenza Viruses ◽  
Receptor Binding Site ◽  
X Ray Crystallography ◽  
Influenza Hemagglutinin ◽  
Health Authorities

H5N1 avian influenza viruses remain a threat to public health mainly because they can cause severe infections in humans. These viruses are widespread in birds, and they vary in antigenicity forming three major clades and numerous antigenic variants. The most important features of the human monoclonal antibody FLD194 studied here are its broad specificity for all major clades of H5 influenza HAs, its high affinity, and its ability to block virus infection, in vitro and in vivo. As a consequence, this antibody may be suitable for anti-H5 therapy and as a component of stockpiles, together with other antiviral agents, for health authorities to use if an appropriate vaccine was not available. Our mutation and structural analyses indicate that the antibody recognizes a relatively conserved site near the membrane distal tip of HA, near to, but distinct from, the receptor-binding site. Our analyses also suggest that the mechanism of infectivity neutralization involves prevention of receptor recognition as a result of steric hindrance by the Fc part of the antibody. Structural analyses by EM indicate that three Fab fragments are bound to each HA trimer. The structure revealed by X-ray crystallography is of an HA monomer bound by one Fab. The monomer has some similarities to HA in the fusion pH conformation, and the monomer’s formation, which results from the presence of isopropanol in the crystallization solvent, contributes to considerations of the process of change in conformation required for membrane fusion.

Sign in / Sign up

Export Citation Format

Share Document