Pyran copolymer antitumor activity

The 1 2 copolymer of dlvlnyl ether and maleic anhydride ("pyran copolymer," I) exhibits a broad range of biological activity, and has been discussed elsewhere in this volume and in earlier reviews (JL, 2) Of particular interest is the polymer s antitumor activity after initial clinical testing and then withdrawal from clinical use due to severe toxicity, the drug is again under evaluation as an agent for the treatment of human cancer. ... 

His research contributions to polymer chemistry span many areas, from studies of alternating copolymers of maleic anhydride and vinyl ether ( pyran copolymer ) having interferon inducing capability and antitumor activity, to polymerization of triazoline diones and synthesis of the antiaromatic 3,3-dimethoxycyclopropene. 

Abstract. Pyran Copolymer (Divema, NSC46015 ), a synthetic polyanion, divinyl ether maleic anhydride copolymer, has achieved clinical trial because of antitumor activity and its role as an anti-viral agent. Most of the previous biologic and clinical work with this agent has been done with pyran copolymer of an average molecular weight of 18000. (NSC46015). 

The Drug Development Branch of the National Cancer Institute and our own laboratories demonstrated antitumor activity for divinyl ether maleic anhydride copolymers. Samples of polycarboxylic divinyl ether maleic anhydride copolymer hydrolysate (NSC 46015 pyran 3,4-dicarboxylic anhydride, tetrahydro-2-methyl-6-(tetrahydro-2,5-dioxo-3-furyl) of average MW 17000 to 36000 show a broad spectrum of antitumor activity against transplanted tumors and a good therapeutic index. 

Methyl vinyl ether-MA copolymer has the property of inducing interferon production in animals, which is potentially useful for inhibiting the growth of Friends leukemia virus.The 2 1 divinyl ether-co-MA polyanion cyclopolymer, often referred to as PYRAN, has had extensive study, because of its antitumor and interferon inducer properties. Many structural modifications and derivatives of this copolymer also exhibit antitumor activity, interferon inducing capacity, and a wide spectrum of biological activity. Recent... 

The polyanions can function as chemical immunomodulators and produce a wide spectrum of effects on the immune system. It was reported that the polyanions have the capacity to activate macrophages, which may be related to their effects on the plasma membrane lipids, and to provide immuno-modulation through B-cell stimulation [8,9]. It was also observed that the antiviral, antibacterial, and antitumor activities of pyran copolymer may be mediated by the induction of interferon (IFN) production [10], macrophage activation [11], or stimulation of antibody-dependent cellular cytotoxicity... 

ADCC) [12]. The low molecular weight pyran copolymer (MVE-2, Mw 15,000) does stimulate natural killer (NK) cells [13,14], Thus, at least two cell types, the macrophages and the NK cells, are presumed to play an important role in the antitumor and antiviral activity of MVE-2. The enhancement of the macrophage and the NK cell activity by these immuno-modulators may have the potential to provide tumoricidal effects and protection against viral infections exacerbated during immunosuppression or immunodeficiency in cases such as acquired immunodeficiency syndrome (AIDS) and severe combined immunodeficiency disease (SCID). 

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