Immunomodulation and antitumor effects of MVE-2 in mice

The biological response modifier maleic anhydride-divinyl ether (MVE-2) can activate natural killer (NK) cells and macrophages and can act as an immunoadjuvant for T and B cells. MVE-2 activates macrophages following intravenous or intraperitoneal injection in a compartmentalized manner, i.e., peritoneal macrophages (i.p. injection) or alveolar macrophages (i.v. injection). It activates NK cells in vivo but not in vitro, a dichotomy that may be secondary to interferon production. Splenic NK cell activity is not prolonged by the multiple injection of MVE-2; instead, it induces a state of NK cell hyporesponsiveness, which may limit its therapeutic efficiency. Therapeutic properties of MVE-2 are largely limited to nonspecific immunoprophylaxis, which may be associated with NK cell activation but which does not necessarily correlate with the level of splenic NK cell activation. Minimal therapeutic efficiency consisting of a slight prolongation in survival is observed in mice with preexistent disease treated with MVE-2. Prolonged survival is observed only in those animals placed on therapy soon after tumor cell challenge (experimental metastasis) and not in mice with established spontaneous metastasis. The need to manipulate the animal model (MVE-2 injection prior to or rapidly following tumor challenge) seems to predict that this agent is unlikely to be clinically useful against preexistent metastatic tumor burden, although some efficiency may be associated with local treatment into the pleural or peritoneal cavity.