PMID: 8608178Nov 1, 1995Paper

IL2-ricin fusion toxin is selectively cytotoxic in vitro to IL2 receptor-bearing tumor cells

Bioconjugate Chemistry
A FrankelM Willingham

Abstract

Fusion toxins consist of peptide ligands linked through amide bonds to polypeptide toxins. The ligand directs the molecule to the surface of target cells and the toxin enters the cytosol and induces cell death. Ricin toxin is an excellent candidate for use in fusion toxins because of its extreme potency, the extensive knowledge of its atomic structure, and the years of experience with RTA chemical conjugates in clinical trials. We synthesized a baculovirus transfer vector with the polyhedrin promoter followed sequentially from the 5' end with DNA encoding the gp67A leader sequence, the tripeptide ADP, IL2, another ADP tripeptide, and RTB. Recombinant baculovirus was generated in Sf9 insect cells and used to infect Sf9 cells. Recombinant IL2-RTB protein was recovered at high yields from day 5 insect cell supernatants, partially purified by affinity chromatography, and characterized. The recombinant product was soluble and immunoreactive with antibodies to RTB and IL2, bound asialofetuin and lactose, and reassociated with RTA. In the presence of lactose to block galactose-binding sites on RTB, the IL2-RTB-RTA heterodimer was selectively cytotoxic to IL2 receptor, bearing cells. Specific cytotoxicity could be blocked with IL2. Thu...Continue Reading

References

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Citations

Dec 24, 1997·Leukemia Research·R J Kreitman
Jun 6, 2000·Advanced Drug Delivery Reviews·I Pastan, R J Kreitman
Jun 10, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S BasakC D Morrow
Nov 16, 2004·Journal of Photochemistry and Photobiology. B, Biology·Roberto LinaresTheresa A Good
Jul 5, 2005·Expert Opinion on Investigational Drugs·R J Kreitman
Sep 2, 2014·Clinical Lymphoma, Myeloma & Leukemia·Andrew C Cannon, Fausto R Loberiza
Oct 26, 2005·Neoplasia : an International Journal for Oncology Research·Khalid A MohamedaliMichael G Rosenblum

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