Hybrid antibodies with dual specificity for the delivery of ricin to immunoglobulin-bearing target cells

Hybrid antibodies possessing one binding site for the toxic lectin ricin and a companion site directed against human immunoglobulin were constructed in vitro. This bifunctional reagent specifically attached to human lymphocyte surface immunoglobulin determinants and, thus situated, could simultaneou...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1981-06, Vol.41 (6), p.2073-2078
Main Authors: Raso, V, Griffin, T
Format: Article
Language:English
Subjects:
Antibodies - immunology
Binding Sites
Carrier Proteins - immunology
Cell Line
Cell Membrane - immunology
Dose-Response Relationship, Drug
Humans
Immunoglobulin G - immunology
Intracellular Membranes - immunology
Lymphocytes - immunology
Protein Biosynthesis
Ribosomes - metabolism
Ricin - immunology
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Summary:Hybrid antibodies possessing one binding site for the toxic lectin ricin and a companion site directed against human immunoglobulin were constructed in vitro. This bifunctional reagent specifically attached to human lymphocyte surface immunoglobulin determinants and, thus situated, could simultaneously capture ricin molecules or its toxic A chain. Attachment of these components to the cell was revealed by specific fluorescein-labeled antibodies. Once concentrated at the target cell membrane, hybrid-bound toxin was subsequently released to function via its normal mechanism of biological action. It gained access to ribosomes, its intracellular target, and curtailed protein synthesis. Toxicity was not augmented for immunoglobulin-negative cells to which hybrid could not bind and free human immunoglobulin G could competitively block the enhanced effects observed for immunoglobulin-bearing cell lines. These results indicate that hybrid antibodies may be utilized to carry active agents within close proximity to the membrane of a specified cell type and thereby selectively enhance their effect.
ISSN:0008-5472