Evaluation of the immunological and toxicological properties of MVE-2 in phase I trials.
Pyran copolymer enhances resistance to infections and transplantable tumors in mice. It induces interferon, activates macrophages, 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 maturation 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.
D000328:Adult; D000368:Aged; D000920:Antibody-Dependent Cell Cytotoxicity; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010314:Partial Thromboplastin Time; D011108:Polymers / Q000009:adverse effects*; D011507:Proteinuria / Q000139:chemically induced; D011517:Prothrombin Time; D011713:Pyran Copolymer / Q000009:adverse effects* / Q000276:immunology
D011108:Polymers; D011713:Pyran Copolymer