Evaluation of the Immunological and Toxicological Properties of MVE-2 in Phase I Trials1

Pyran copolymer enhances resistance to infections and transplantable tumors in mice. It induces interferon, activates macro phages, increases antibody-dependent cellular cytotoxicity (ADCC), functions as an adjuvant, and has direct antitumor effects. MVE-2, a low-molecular-weight (15,000) component of pyran copolymer, exhibited less toxicity and essentially the same positive biological effects as pyran copolymer. MVE-2 was, therefore, chosen for clinical trials. This study was designed to determine the toxicity and immunological effects of MVE-2 in humans. Fourteen patients who received biweekly MVE-2 had lymphocyte and monocyte ADCC, natural killer activity, and monocyte to macrophage maturation measured 2, 3, 7,10, and 13 days after each of the first three doses of MVE-2. Lymphocyte antibody-dependent cellular cytotoxicity and monocyte matura tion increased significantly following MVE-2 administration and the effect persisted at least 4 weeks. Although numbers were small, the enhanced ADCC seemed related to both single dose and cumulative dose of MVE-2. Five of six patients receiving more than 2 g of MVE-2 had improvement in lymphocyte ADCC. Increases in lymphocyte and monocyte natural killer activity approached, but did not attain statistical significance. Proteinuria was the dose-limiting toxicity, but was reversible. MVE-2 induced a modest, but real enhancement of lymphocyte and monocyte function at doses that were well tolerated.