PROPHYLACTIC INTERVENTION IN RADLV-INDUCED LYMPHOMAGENESIS WITH AN ANTI-IL-4 MONOCLONAL-ANTIBODY

Intrathymic inoculation of the radiation leukemia virus (RadLV) into C 57BL/6 mice induces thymic lymphomas after 4-6 months. During premalig nant latency, a population of RadLV-infected prelymphoma (PL) cells (w hose survival is dependent on autostimulation with IL-4) persists in t he thymus. PL cells explanted from RadLV-inoculated mice can be propag ated in cultures containing IL-4, and in vitro growth of PL cells is e ffectively inhibited by anti-IL-4 antibodies. We subjected RadLV-inocu lated mice to prophylactic treatment with anti-IL-4 antibodies and a v irus-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 agains t lymphoma. These results demonstrate the effectiveness of prophylacti c intervention during premalignancy by using antagonists that restrain the growth of PL cells.