Compositions of engineered human arginases and methods for treating cancer

摘要

Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.

主权项

1. A composition comprising an isolated human Arginase I mutant and a cobalt metal cofactor, said mutant having at least one amino acid substitution that is a Ser residue substituted for an Asp residue normally found at position 181 of human Arginase I of SEQ ID NO:13 (Asp181Ser), a Cys residue substituted for a Ser residue normally found at position 230 of human Arginase I (Ser230Cys), a Gly residue substituted for the Ser residue normally found at position 230 of human Arginase I (Ser230Gly), a Phe residue substituted for a Cys residue normally found at position 303 of human Arginase I (Cys303Phe), an Be residue substituted for a Cys residue normally found at position 303 of human Arginase I (Cys303Ile), or a Glu residue substituted for the Asp residue normally found at position 181 and an Ala residue substituted for the Ser residue normally found at position 230 of human Arginase I (Asp181Glu/Ser230Ala), the composition being at physiological pH.