Successful immunotherapy of @entity19 experimental hepatic XXXX with lymphokine-activated killer cells and recombinant @entity2047 .

@entity2047 @entity19 @entity5 @entity409 @entity3 @entity526 @entity27262
Lymphokine-activated killer (LAK) cells are generated in vitro by the incubation of normal @entity19 splenocytes in @entity2047 . We have shown previously that the systemic injection of LAK cells in conjunction with recombinant @entity2047 can reduce the number of established pulmonary @entity3 in @entity19 . In an attempt to study this approach in the treatment of hepatic @entity3 , we developed a technique for the induction of hepatic @entity3 in @entity19 based on the intrasplenic injection of @entity5 cells and have tested the effects of LAK cells and recombinant @entity2047 produced in @entity526 ( @entity27262 ) therapy on these @entity3 . Treatment with LAK cells alone in 14 consecutive experiments rarely produced significant reduction in @entity3 over control (mean percentage reduction, 12%). Therapy with @entity27262 alone produced a dose-dependent @entity409 . In 20 consecutive experiments when @entity27262 was administered i.p. three times a day at doses varying from 1,000 to 5,000, 10,000 to 15,000, and 25,000 units, a statistically significant (P less than 0.05) reduction in liver @entity3 was seen in 2 of 12, 2 of 4, and 8 of 12 determinations, respectively (percentage reduction, 0 to 97; mean, 42%). At doses greater than 25,000 units, the reduction in @entity3 was highly reproducible (percentage reduction, 66 to 95; mean, 83%) and was statistically significant in 14 of 14 determinations. When LAK cells were given i.v. in addition to @entity27262 administration in 16 consecutive experiments, the percentage reduction in liver @entity3 was markedly increased over that seen with @entity27262 alone (mean percentage reduction, 77% at doses of 5,000 to 25,000 units of @entity27262 and mean reduction, 97% for doses greater than 25,000 units of @entity27262 ). At doses of 5,000, 10,000, 25,000, and greater than 25,000 units of @entity27262 plus LAK cells, significant reduction of liver @entity3 (P less than 0.05) was achieved in 3 of 7, 2 of 2, 8 of 8, and 6 of 6 determinations, respectively. When animals were given fresh splenocytes or splenocytes cultured in complete medium without @entity27262 instead of LAK cells, no reduction in liver @entity3 was seen except for that attributable to the administration of @entity27262 alone. Sublethal total body irradiation of the @entity19 prior to therapy abrogated the therapeutic effects of @entity27262 , but the effects of treatment with LAK cells plus @entity27262 were maintained. Thus, treatment with @entity27262 alone or in combination with LAK cells is effective in reducing the number of established hepatic micrometastases in a @entity19 model.(ABSTRACT TRUNCATED AT 400 WORDS)
