A large number of naturally occurring polyanionic materials are known, each of which possesses its own set of physiological properties. In recent years, a wide variety of synthetic polyanions have become available, and investigators have compared their physiological properties with the naturally occurring polyanions. Perhaps the most widely investigated synthetic polyanion is the 1:2 regularly alternating cyclocopolymer (DIVEMA (also commonly known as """"""""Pyran Copolymer"""""""") of divinyl ether (DVE) and maleic anhydride (MA), first discovered in the University of Florida laboratories. This material has been extensively investigated, both from the standpoint of its chemical structure and its biological activity, and it has been shown to possess a wide spectrum of biological activity. It possesses anti-tumor activity and is an interferon inducer. It also possesses antibacterial, antiviral, antifungal, anticoagulant, and antiarthritic properties, and inhibits reverse transcriptase, activates macrophages, and is capable of effecting elimination of plutonium. During a study of the relationship of structure to biological properties of DIVEMA and related copolymers, we synthesized fifty-eight copolymers which were evaluated by the National Cancer Institute of NIH for screening against a variety of tumors. Fifteen of these copolymers were found to be effective against one or more tumors included in the NCI tests. Subsequent to these investigations, a study of molecular weight and molecular weight distribution of DIVEMA has shown that its effectiveness as an anti-tumor agent is vastly improved when prepared at an average molecular weight of 15,000 and with narrow molecular weight distribution. The material, supplied by Adrian Laboratories, is now being investigated clinically. The purpose of this investigation is to study the effect of molecular weight and molecular weight distribution on the anti-tumor activity of the fifteen copolymers referred to above.
