EFFECT OF HUMAN NATURAL-KILLER-CELLS ON THE METASTATIC GROWTH OF HUMAN-MELANOMA XENOGRAFTS IN MICE WITH SEVERE COMBINED IMMUNODEFICIENCY

An in vivo model for human melanoma was established with the growth of CR3 and DE5 human melanoma tumor cells following i.v. injection into C.B-17 severe combined immunodeficient mice depleted of murine natural killer (NK) cells. The ability of human NK cells to mediate antitumor activity in vivo was investigated by evaluating the number of lung no dules and survival of mice given injections of human NK cells i.v. ear ly after injection of CR3 tumor cells. Under these conditions, human N K cells effectively reduced lung nodule counts and prolonged survival when coinjected with interleukin 2 (IL-2). Multiple injections of IL-2 given during the first 16 h post-NK injection did not further enhance the tumor reduction. Significantly increased antitumor activity again st CR3 tumor cells in vivo was observed in mice receiving NK cells coi njected with IL-2 and interleukin 12 (IL-12) in comparison to NK cells and IL-2 only. However, coinjection of IL-12 with human NK cells alon e did not reduce the tumor burden. These results demonstrate the antit umor activity of human NK cells against human melanoma in severe combi ned immunodeficient mice and its augmentation by IL-2, alone or in com bination with IL-12, suggesting that this model can be used to further investigate the interaction between human NK cells and human tumors.