Wynnewood, PA, United States
Wynnewood, PA, United States
SEARCH FILTERS
Time filter
Source Type

Puligedda R.D.,Lankenau Institute for Medical Research | Kouiavskaia D.,U.S. Food and Drug Administration | Adekar S.P.,Lankenau Institute for Medical Research | Adekar S.P.,Immunome | And 7 more authors.
Antiviral Research | Year: 2014

An essential requirement for eradication of poliomyelitis is the elimination of circulating vaccine derived polioviruses (cVDPV) and polioviruses excreted by chronically infected individuals with immunodeficiencies (iVDPV). As part of a post-eradication risk management strategy, a human monoclonal antibody (mAb) therapeutic could play a role in halting excretion in asymptomatic carriers and could be used, in combination with vaccines and antiviral drugs, to protect polio-exposed individuals. Cross-neutralizing mAbs may be particularly useful, as they would reduce the number of mAbs needed to create a comprehensive PV therapeutic. We cloned a panel of IgG mAbs from OPV-vaccinated, IPV-boosted healthy subjects. Many of the mAbs had potent neutralizing activities against PV wild-type (WT) and Sabin strains, and two of the mAbs, 12F8 and 1E4, were significantly cross-reactive against types 1 and 2 and types 1 and 3, respectively. Mapping the binding epitopes using strains resistant to neutralization (escape mutants) suggested that cross-specific PV binding epitopes may primarily reside within the canyon region, which interacts with the cellular receptor molecule CD155 and the cross-neutralizing chimpanzee/human mAb, A12. Despite their close proximity, the epitopes for the 12F8 and 1E4 mAbs on Sabin 1 were not functionally identical to the A12 epitope. When tested together, 12F8 and 1E4 neutralized a diverse panel of clinically relevant PV strains and did not exhibit interference. Virus mutants resistant to the anti-poliovirus drug V-073 were also neutralized by the mAbs. The 12F8 and 1E4 mAbs may suitable for use as anti-PV therapeutics. © 2014 Published by Elsevier B.V.


Sharma R.,Lankenau Institute for Medical Research | Zhao H.,Immunome | Al-Saleem F.H.,Inventox, Llc | Ubaid A.S.,Lankenau Institute for Medical Research | And 11 more authors.
Molecular Immunology | Year: 2014

Immune complexes formed between monoclonal antibodies (mAbs) and toxins can neutralize toxicity in vivo by multiple mechanisms. Toxin sequestration and clearance by mAbs may be improved by enhancing their ability to bind to red blood cells (RBCs) through immune adherence. This can be achieved by converting the mAbs to heteropolymers (HPs), which are antigen-specific mAbs cross-linked to mAbs targeting the complement receptor (CR1), a protein that is expressed on the surface of RBCs in primates and mediates delivery of complement C3b-containing immune complexes to tissue macrophages. Conversion of mAbs to HPs has been shown to enhance clearance of multivalent antigens from the blood circulation, but the interaction of HPs with monovalent toxins has not been examined. Using botulinum neurotoxin (BoNT) as a model system, we studied the effect of conversion of a pair of BoNT-specific mAbs into HPs on toxin neutralization and handling in vivo. Two HPs given in combination had 166-fold greater potency than un-modified mAbs, neutralizing 5000 LD50 BoNT, when tested in transgenic mice expressing human CR1 on RBC membranes. Improvement required adherence of BoNT to the RBC in vivo and 2 HPs, rather than an HP. +. mAb pair. The HP pair bound BoNT to RBCs in the circulation for 2. h, in comparison to BoNT-neutralizing anti-serum, which induced no detectable RBC binding. HP pairs exhibited enhanced uptake by peritoneal macrophages in vitro, compared to pairs of mAbs or mAb. +. HP pairs. In a post-exposure therapeutic model, HPs gave complete protection from a lethal BoNT dose up to 3. h after toxin exposure. In a pre-exposure prophylaxis model, mice given HP up to 5 days prior to BoNT administration were fully protected from a lethal BoNT dose. These studies elucidate general mechanisms for the neutralization of toxins by HP pairs and demonstrate the potential utility of HPs as BoNT therapeutics. © 2013 The Authors.


Adekar S.P.,Lankenau Institute for Medical Research | Adekar S.P.,Immunome | Adekar S.P.,Augmenta | Segan A.T.,Lankenau Institute for Medical Research | And 8 more authors.
PLoS ONE | Year: 2011

Botulinum neurotoxin (BoNT) potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC) in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP) to link biotinylated molecules to glycophorin A (GPA) on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo. © 2011 Adekar et al.


Trademark
Immunome | Date: 2016-05-31

Monoclonal antibodies for medical and scientific research; antibodies and immunoconjugates for medical and scientific research; proteins and components of proteins for medical and scientific research; cells, cell extracts and components of cells for medical and scientific research. Monoclonal antibodies and immunoconjugates for medical or clinical use; pharmaceutical compositions comprising monoclonal antibodies for use in the diagnosis, prevention, management and treatment of oncological, neurological, infectious disease, metabolic, viral, endocrine, musculoskeletal, cardiovascular, cardiopulmonary, genitourinary, sexual dysfunction, hepatological, opthalmic, respiratory, gastrointestinal, hormonal, dermatological, psychiatric and immune system related conditions, diseases and disorders; pharmaceutical compositions comprising immunoconjugates in the diagnosis, prevention, management and treatment of oncological, neurological, infectious disease, metabolic, viral, endocrine, musculoskeletal, cardiovascular, cardiopulmonary, genitourinary, sexual dysfunction, hepatological, opthalmic, respiratory, gastrointestinal, hormonal, dermatological, psychiatric and immune system related conditions, diseases and disorders; cells, cell extracts and components of cells for medical or clinical use; pharmaceutical preparations for use in the diagnosis, prevention, management and treatment of oncological, neurological, infectious disease, metabolic, viral, endocrine, musculoskeletal, cardiovascular, cardiopulmonary, genitourinary, sexual dysfunction, hepatological, opthalmic, respiratory, gastrointestinal, hormonal, dermatological, psychiatric and immune system related conditions, diseases and disorders; diagnostic preparations for medical use; diagnostic kits comprising reagents for medical and clinical use. Biotechnology services, namely, development of monoclonal antibodies; pharmaceutical, medical, scientific, biopharmaceutical and biotechnology research and development; drug discovery services; providing medical and scientific research information in the field of medicine and pharmaceuticals.


Immunome | Entity website

Effective: November 30, 2015 Acceptance of the Terms and Conditions. Immunome, Inc ...


Immunome | Entity website

This Privacy Policy was last updated on November 30, 2015. Our Policy: Welcome to the web site (the Site) of Immunome, Inc ...

Loading Immunome collaborators
Loading Immunome collaborators