Antibody to Ricin A Chain Hinders Intracellular Routing of Toxin and Protects Cells Even after Toxin Has Been Internalized

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Antibody to Ricin A Chain Hinders Intracellular Routing of Toxin and Protects Cells Even after Toxin Has Been Internalized

BACKGROUND Mechanisms of antibody-mediated neutralization are of much interest. For plant and bacterial A-B toxins, A chain mediates toxicity and B chain binds target cells. It is generally accepted and taught that antibody (Ab) neutralizes by preventing toxin binding to cells. Yet for some toxins, ricin included, anti-A chain Abs afford greater protection than anti-B. The mechanism(s) whereby ...

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

PB10 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 potent in vitro and in vivo toxin-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 d...

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Endocytosis and intracellular routing of an antibody-ricin A chain conjugate.

An immunotoxin (IT) was prepared from monoclonal antibody (MoAb) 115D8 and ricin A chain. MoAb 115D8 is directed against the carcinoma-associated sialomucin MAM-6. In a protein synthesis inhibition assay this IT was cytotoxic for the human breast cancer cell line T47D. Using postembedding immunoelectron microscopy the binding and intracellular routing of the IT in T47D cells were studied by sim...

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Antibody-Mediated Inhibition of Ricin Toxin Retrograde Transport

Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the trans-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies preve...

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ژورنال

عنوان ژورنال: PLoS ONE

سال: 2013

ISSN: 1932-6203

DOI: 10.1371/journal.pone.0062417