ADMINISTRATION OF KYNURENINE DEPLETING ENZYMES FOR TUMOR THERAPY

摘要

Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids.

主权项

1. An isolated, modified human kynureninase enzyme, said modified enzyme having at least one substitution relative to native human kynureninase (see SEQ ID NO: 8), said at least one substitution is at a position selected from the group consisting of: (a) A99, F306, and A436; (b) A99, G112, F306, L337, I405, S408; (c) G112, F306, L337, and I405; (d) A99, T138, F306, and A436; (e) A99, G112, F306, V339, I405, and S408; (f) A99 and F306; (g) F306, L337, V339, I405, and S408; (h) G112, F306, V339, and I405; (i) G112, F306, V339, S408; (k) F71, A99, G112, T138, F306, L337, V339, I405, S408, and A436; (1) A99, G112, F306, L337, V339, I405, and S408; (m) A436; (n) A99, G112, T138, V339, and I405; (p) A99, G112, F306, I405, S408, and A436; (q) F71, A99, I131, F249, and L322; (r) A99, I131, F249, E259, and F306; (s) F71, A99, and E259; (t) F71, A99, S167, and E259; (u) I131, F249, and S274; (v) L59, G112, F306, V339, I405, and S408; (w) I110 and F306; (x) A99, I131, F249, and E259; (y) F71, E259, and L322; (z) H41, Q175, and A436; (a′) A99, I131, and F249; (b′) I131 and F249; (c′) T138 and A436; (d′) T138; (e′) F71, A99, I131, E259, and V303; (f) A99, G112, F306, V339, I405, and S408; (g′) F71, A99, I131, E259, and A282; (h′) F71, F249, E259, and V303; (i′) I110; and (j′) F306.