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Hybrid Antibodies with Dual Specificity for the Delivery of Ricin to Immunoglobulin-bearing Target Cells¹

Divisions of Tumor Immunology and Pharmacology, Sidney Farber Cancer Institute, Boston, Massachusetts 02115

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.

¹ This work was supported in part by Grants CA 06516 and CA 19589 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

³ Present address: University of Massachusetts Medical School, Worchester, Mass. 01603.

Received 11/ 6/80. Accepted 2/19/81.

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