Prophylactic intervention in RadLV-induced lymphomagenesis with an anti-IL-4 monoclonal antibody.
Intrathymic inoculation of the radiation leukemia virus (RadLV) into C57BL/6 mice induces thymic lymphomas after 4-6 months. During premalignant latency, a population of RadLV-infected prelymphoma (PL) cells (whose survival is dependent on autostimulation with IL-4) persists in the thymus. PL cells explanted from RadLV-inoculated mice can be propagated in cultures containing IL-4, and in vitro growth of PL cells is effectively inhibited by anti-IL-4 antibodies. We subjected RadLV-inoculated mice to prophylactic treatment with anti-IL-4 antibodies and a virus-specific immunotoxin (IT). Administration of IT delayed the onset of lymphoma but was not curative. Anti-IL-4 antibodies had a similar effect when administered at low doses. High doses of anti-IL-4, given 3-5 weeks after virus inoculation, provided complete protection against lymphoma. These results demonstrate the effectiveness of prophylactic intervention during premalignancy by using antagonists that restrain the growth of PL cells.
Epzsteyn
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Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Vitetta
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ES
Yefenof
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D015847:Interleukin-4 / Q000502:physiology*; D008223:Lymphoma / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D016721:Radiation Leukemia Virus; D012192:Retroviridae Infections / Q000517:prevention & control*; D014412:Tumor Virus Infections / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D015847:Interleukin-4