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Abrin Immunotoxin: Targeted Cytotoxicity and Intracellular Trafficking Pathway

Gadadhar, Sudarshan and Karande, Anjali A (2013) Abrin Immunotoxin: Targeted Cytotoxicity and Intracellular Trafficking Pathway. In: PLOS ONE, 8 (3).

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Official URL: http://dx.doi.org/10.1371/journal.pone.0058304

Abstract

Background: Immunotherapy is fast emerging as one of the leading modes of treatment of cancer, in combination with chemotherapy and radiation. Use of immunotoxins, proteins bearing a cell-surface receptor-specific antibody conjugated to a toxin, enhances the efficacy of cancer treatment. The toxin Abrin, isolated from the Abrus precatorius plant, is a type II ribosome inactivating protein, has a catalytic efficiency higher than any other toxin belonging to this class of proteins but has not been exploited much for use in targeted therapy. Methods: Protein synthesis assay using (3)H] L-leucine incorporation; construction and purification of immunotoxin; study of cell death using flow cytometry; confocal scanning microscopy and sub-cellular fractionation with immunoblot analysis of localization of proteins. Results: We used the recombinant A chain of abrin to conjugate to antibodies raised against the human gonadotropin releasing hormone receptor. The conjugate inhibited protein synthesis and also induced cell death specifically in cells expressing the receptor. The conjugate exhibited differences in the kinetics of inhibition of protein synthesis, in comparison to abrin, and this was attributed to differences in internalization and trafficking of the conjugate within the cells. Moreover, observations of sequestration of the A chain into the nucleus of cells treated with abrin but not in cells treated with the conjugate reveal a novel pathway for the movement of the conjugate in the cells. Conclusions: This is one of the first reports on nuclear localization of abrin, a type II RIP. The immunotoxin mAb F1G4-rABRa-A, generated in our laboratory, inhibits protein synthesis specifically on cells expressing the gonadotropin releasing hormone receptor and the pathway of internalization of the protein is distinct from that seen for abrin.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to the PUBLIC LIBRARY SCIENCE, USA.
Department/Centre: Division of Biological Sciences > Biochemistry
Depositing User: Francis Jayakanth
Date Deposited: 12 Apr 2013 11:14
Last Modified: 12 Apr 2013 11:14
URI: http://eprints.iisc.ac.in/id/eprint/46387

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