Effect of combined therapy with lymphokine-activated killer cells, interleukin 2 and specific monoclonal antibody on established B16 melanoma lung metastases.

We have previously shown that treatment of C57BL/6 mice with specific anti-B16 melanoma monoclonal antibody (Mab) significantly reduced the number of established liver metastases. In this paper we show that when treatment with Mab was applied to mice bearing both liver and lung micrometastases, the number of liver metastases was reduced by 72-98%, whereas no effect was seen on the number of lung metastases. In contrast to results obtained when treating liver metastases, treatment of B16 melanoma lung metastases with Mab and recombinant interleukin 2 was unsuccessful when recombinant interleukin 2 was given concomitantly or after priming with high doses of recombinant interleukin 2. In contrast, when therapy with anti-B16 Mab was combined with the administration of C3H lymphokine-activated killer (LAK) cells, which were shown to exhibit antibody dependent cellular cytotoxicity (ADCC) activity, a significant enhancement in the antitumor efficacy of LAK cells was seen. The inability of C57BL/6 LAK cells, which exhibited low if any ADCC activity to mediate a similar effect, suggested that an ADCC-like mechanism was involved in this therapy. The effect of C3H LAK cells was apparently not the result of administration of allogeneic cells, since fresh C3H splenocytes had no effect on lung metastases when given together with Mab. These findings demonstrate the potential of specific antitumor Mab to affect not only established liver metastases but, when combined with LAK cells that mediate ADCC activity to enhance the eradication of lung metastases as well.