Inhibition of experimental tumor metastasis by selective activation of natural killer cells

The antitumor activity generated by selective activation of natural killer (NK) cells was studied in vitro and in vivo. Unlike Corynebacterium parvum CN6134, which activated both NK cells and macrophages, periodate-oxidized C. parvum CN6134 lost the ability to activate macrophages but retained almost all the NK-stimulating capacity of the untreated bacterium. The "inactive" C. parvum strain CN5888 also induced a modest, but selective, activation of NK cells. The enhanced NK cell-mediated cytotoxicity was expressed against YAC-1 lymphoma, UV-2237 fibrosarcoma, and B16 melanoma target cells in vitro and was manifested in vivo by increased destruction of circulating tumor cells and the inhibition of hematogenous tumor metastasis. Periodate-treated C. parvum was as effective in inhibiting the formation of B16 melanoma pulmonary metastases as was untreated C. parvum. In both cases, the inhibiting effect corresponded closely with the kinetics of NK cell activation.