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 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 against the Enzymatic Subunit of Ricin Toxin Rescues Rhesus macaques from the Lethality of Aerosolized Ricin

2018 ◽  
Author(s):  
Chad J. Roy ◽  
Dylan J. Ehrbar ◽  
Natasha Bohorova ◽  
Ognian Bohorov ◽  
Do Kim ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Therapeutic Potential ◽  
Rhesus Macaques ◽  
Lethal Dose ◽  
Drug Candidate ◽  
Antibody Treatment ◽  
Ricin Toxin ◽  
Humanized Monoclonal Antibody ◽  
Before And After ◽  
A Chain

AbstractRicin toxin (RT) ranks at the top of the list of potential bioweapons of concern to civilian and military personnel alike due to its high potential for morbidity and mortality after inhalation. In non-human primates, aerosolized ricin triggers a severe acute respiratory distress characterized by perivascular and alveolar edema, neutrophilic infiltration, and severe necrotizing bronchiolitis and alveolitis. There are currently no approved countermeasures for ricin intoxication. In this report, we demonstrate the therapeutic potential of huPB10, a toxin-neutralizing humanized monoclonal antibody (MAb) against an immunodominant epitope on ricin’s enzymatic A chain (RTA). Five rhesus macaques that received intravenous huPB10 (10 mg/kg) four hours after lethal dose ricin aerosol exposure all survived the toxin challenge, as compared to control animals, which succumbed to ricin intoxication within 30 h. Antibody treatment at 12 h after ricin exposure resulted in the survival of only one of five monkeys, indicating that, in the majority of animals, ricin intoxication and local tissue damage had progressed beyond the point where huPB10 intervention was beneficial. Change in pro-inflammatory cytokine/chemokines levels in bronchial alveolar lavage fluids before and after toxin challenge successfully clustered monkeys based on survival, as well as treatment group. IL-6 was the most apparent marker of ricin intoxication. This study represents the first demonstration in nonhuman primates that the lethal effects of inhalational ricin exposure can be negated by a drug candidate and opens up a path forward for product development.

scholarly journals An intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation

2019 ◽  
Vol 16 (4) ◽  
pp. 793-807 ◽  
Author(s):  
Yinghui Rong ◽  
Fernando J. Torres-Velez ◽  
Dylan Ehrbar ◽  
Jennifer Doering ◽  
Renjie Song ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tissue Damage ◽  
Pulmonary Tissue ◽  
Ricin Toxin ◽  
Antibody Cocktail

scholarly journals A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease

2016 ◽  
Vol 131 ◽  
pp. 92-99 ◽  
Author(s):  
Amanda E. Calvert ◽  
Kandice L. Dixon ◽  
Joseph Piper ◽  
Susan L. Bennett ◽  
Brett A. Thibodeaux ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mouse Model ◽  
Yellow Fever ◽  
Virus Strain ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Humanized Monoclonal Antibody

scholarly journals SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies

2017 ◽  
Vol 11 (12) ◽  
pp. e0006133 ◽  
Author(s):  
Tzu-Yuan Chao ◽  
Shiqi Ren ◽  
Enyun Shen ◽  
Susan Moore ◽  
Shou-feng Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Humanized Monoclonal Antibody ◽  
Exposure Prophylaxis ◽  
Antibody Cocktail

scholarly journals Clearance Kinetics and External Dosimetry of 131I-Labeled Murine and Humanized Monoclonal Antibody A33 in Patients with Colon Cancer: Radiation Safety Implications

2009 ◽  
Vol 96 (5) ◽  
pp. 550-557 ◽  
Author(s):  
Lawrence T. Dauer ◽  
Daniel C. Boylan ◽  
Matthew J. Williamson ◽  
Jean St. Germain ◽  
Steven M. Larson
Keyword(s):  
Monoclonal Antibody ◽  
Colon Cancer ◽  
Radiation Safety ◽  
Humanized Monoclonal Antibody ◽  
Clearance Kinetics

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.

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