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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jan 15;89(2):728–732. doi: 10.1073/pnas.89.2.728

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

E Yefenof 1, G Abboud 1, S Epszteyn 1, E S Vitetta 1
PMCID: PMC48312  PMID: 1731346

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 prophylactically 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.

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Selected References

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