Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin.
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.
Yefenof
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E
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassa Medical School, Jerusalem, Israel.
Abboud
G
G
Epszteyn
S
S
Vitetta
E S
ES
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D015686:Gene Products, env / Q000276:immunology; D000922:Immunotoxins / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000378:metabolism; D008223:Lymphoma / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D011289:Preleukemia / Q000628:therapy*; D016721:Radiation Leukemia Virus / Q000276:immunology; D016019:Survival Analysis; D013950:Thymus Gland / Q000502:physiology; D013953:Thymus Neoplasms / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D015686:Gene Products, env; D000922:Immunotoxins; D015847:Interleukin-4; D016572:Cyclosporine