Compositions and methods for amino acid depletion therapy

Abstract

Compositions and methods for the preparation of high purity arginase and high efficiency preparation of monosubstituted polyethylene glycol conjugation of arginase are provided, as are methods for using arginase in combination with asparaginase to inhibit cancer cells. High purity arginase is provided by applying an initial high temperature precipitation step, followed by ion exchange to provide arginase at a purity of 90% or greater. Conjugation with either linear or branched polyethylene glycol is performed using a maleimide-derivatized polyethylene glycol at low molar excess relative to arginase and at reduced temperature. Such polyethylene glycol-derivatized arginase is useful in combination with asparaginase in inhibiting the growth of cancer cells, particularly cells that have low endogenous asparaginase expression.

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