IL2-Ricin Fusion Toxin is Selectively Cytotoxic in Vitro to IL2 Receptor-Bearing Tumor Cells

Arthur Frankel, Edward Tagge, John Chandler, Chris Burbage, Greg Hancock, Joseph Vesely, Mark Willingham

Research output: Contribution to journalArticle

11 Scopus citations

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 galactosebinding sites on RTB, the IL2-RTB-RTA heterodimer was selectively cytotoxic to IL2 receptor, bearing cells. Specific cytotoxicity could be blocked with IL2. Thus, we report a novel targeted plant toxin fusion protein with full biological activity.

Original languageEnglish (US)
Pages (from-to)666-672
Number of pages7
JournalBioconjugate Chemistry
Volume6
Issue number6
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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    Frankel, A., Tagge, E., Chandler, J., Burbage, C., Hancock, G., Vesely, J., & Willingham, M. (1995). IL2-Ricin Fusion Toxin is Selectively Cytotoxic in Vitro to IL2 Receptor-Bearing Tumor Cells. Bioconjugate Chemistry, 6(6), 666-672. https://doi.org/10.1021/bc00036a002