Both macrophages and natural killer cells have been implicated in the antimetastatic activity of
maleic anhydride-divinyl ether (MVE-5). In the present study, we attempted to utilize anti-asialo-GM1 antibody and
2-chloroadenosine, agents that kill natural killer (NK) cells and macrophages, respectively, to determine the relative contribution of each effector cell type to the overall host defense. These agents were tested in the M109 lung
metastasis model in syngeneic BALB/c mice, and the cytotoxic activities of both peritoneal macrophages and splenic NK cells were followed. The most profound antitumor effect was observed when
MVE-5 was given before rather than after i.v.
tumor inoculation. Treatment i.p. with
MVE-5 at 20 mg/kg produced greater than 98% inhibition of subsequent lung
metastases when given 2 days prior to
tumor. Anti-asialo-GM1 antibody (25 mg/kg, i.p.) and
2-chloroadenosine (50 mg/kg, i.p.) were administered concurrently with
MVE-5. Although each agent exhibited greater selectivity for its respective target, the early (Day 2) inhibitory response was nonspecific. By Day 5 after
MVE-5 treatment,
2-chloroadenosine only inhibited macrophage tumoricidal activity, and conversely, anti-asialo-GM1 antibody only inhibited NK reactivity. Despite the ability of these agents to increase survival of
metastases in control animals, they only slightly abrogated the antimetastatic activity of
MVE-5. Our data suggest that caution should be exercised in using these agents to discriminate macrophage and NK responses.