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We investigated beneficial effects of AIT with anticancer agents on survival of subcutaneous tumor-bearing mice and suppression of artificial lung metastasis, and optimal schedule of administration of each treatment in vivo. 7-8 weeks old C 57 BL/6 mice were inoculated s.c. with 5 x 10(6) B 16 melanoma cells, or i.v. with 2 x 10(5) B 16-F 10 melanoma cells. Mouse splenocytes were cultured with 3.5 x 10(3) JRU/ml interleukin 2 for 14 days, and induced LAK cells were harvested. Anticancer agents (Cx), CDDP or MMC were given i.p. in mice. 1 x 10(7) or 5 x 10(7) LAK cells were given either s.c. around the tumor or i.v. respectively, and 1.4 x 10(5) JRU/mouse IL-2 was administered s.c. for 6 days after LAK cell injection. Therapy groups were as follows #1: Cx day 3, AIT day 3-8. #2: Cx day 3, AIT day 6-11, #3: Cx day 8, AIT day 3-8. In therapy groups #1 and #2, we observed additive effects of AIT and anti-cancer agents in life-prolongation and suppression of lung metastasis. It was also shown that LAK induction in vivo was augmented by anticancer agents in groups #1 and #2, which might represent one of the mechanisms behind observed additive effects. Furthermore, our results suggest that therapeutic effects of the combination of AIT and anticancer agents depend on the schedule of administration.

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Combined effect of adoptive immunotherapy(AIT) with lymphokine-activated killer(LAK) cells and interleukin-2(IL-2) and chemotherapy in tumor-bearing mice.