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.