Treatment of premalignancy: Prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin

Eitan Yefenof, Ghada Abboud, Sergio Epszteyn, Ellen S. Vitetta

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Radiation leukemia virus (RadLV)-induced preleukemic (PL) latency is characterized by the appearance of virus-infected PL cells in the thymus. The survival of these PL cells is dependent upon autostimulation with interleukin 4 (IL-4). We have intervened prophytactically in RadLV-induced preleukemia by using cyclosporin-A (CSA), which inhibits IL-4 production, and an immunotoxin (ITx) that kills PL cells. CSA efficiently inhibited IL-4 secretion from RadLV-induced PL and leukemic cells, and its administration to PL mice caused a significant delay in their death. An ITx consisting of anti-RadLV glycoprotein-70 (gp70) antibody coupled to ricin A chain efficiently inhibited protein synthesis in virus-infected cells in vitro and, when injected into PL mice, also delayed their death. Combined treatment with CSA and ITx prevented 75% of the treated PL mice from developing lymphoma. These results show that the development of malignancy from a premalignant state can be averted by a combination of therapeutic modalities that decrease the size and growth rate of the premalignant cell population.

Original languageEnglish (US)
Pages (from-to)728-732
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number2
DOIs
StatePublished - 1992

Keywords

  • Interleukin 4
  • Lymphokine
  • Malignancy
  • Preleukemia
  • Thymoma

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Treatment of premalignancy: Prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin'. Together they form a unique fingerprint.

Cite this