Potent antitumor effects of an antitumor endothelial cell immunotoxin in a murine vascular targeting model

Francis J. Burrows, Jay P. Overholser, Philip E. Thorpe

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Immunotoxins and other antibody-based therapeutic reagents have proved effective against lymphomas and leukemias, but results with carcinomas and other solid tumors have thus far been less impressive. A major reason for this difference is that macromolecules penetrate poorly and unevenly into solid tumors. A solution to this problem would be to attack the endothelial cells of the tumor vascular bed rather than the tumor cells themselves. We have developed a murine model of this vascular targeting approach where transfection of the tumor cells with a cytokine gene causes them to induce the expression of an experimental marker (MHC Class II) on tumor endothelium. In this report we show that an anti-Class II-deglycosylated Ricin A-chain immunotoxin kills IFN-γ-activated endothelial cells in culture and, when injected into tumor-bearing Balb/c nude mice, causes complete thrombosis of the tumor vasculature, widespread infarction, and dramatic regressions of large solid tumors. These findings suggest that immunoconjugates prepared with recently described antibodies against human tumor endothelium could provide a broadbased therapy for variety of solid cancers in humans.

Original languageEnglish (US)
Pages (from-to)15-25
Number of pages11
JournalCell Biophysics
Volume24-25
Issue number1-3
DOIs
StatePublished - Jan 1 1994

Keywords

  • Solid tumor
  • antibody
  • endothelial cells
  • immunotoxin
  • therapy

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology

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