Antibody being capable of binding to transforming growth factor alpha and having growth-suppressing activity on cancers having Ras gene mutation

摘要

It has been found out that among antibodies showing reactivity with wild type TGF-α, antibodies less reactive with G79A-substituted TGF-α have an excellent growth-suppressing effect on cancer cells having a mutated Ras gene. Further, it has been found out that most of these antibodies have an activity of inhibiting EGFR tyrosine phosphorylation and/or an induction-suppressing activity on vascular endothelial cells.

主权项

1. An antibody that specifically binds to human TGF-α, wherein the antibody comprises any one of the following characteristics (a) to (h):
(a) a light chain variable region including the amino acid sequences of SEQ ID NOs: 19 to 21, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 22 to 24; (b) a light chain variable region including the amino acid sequences of SEQ ID NOs: 25 to 27, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 28 to 30; (c) a light chain variable region including the amino acid sequences of SEQ ID NOs: 31 to 33, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 34 to 36; (d) a light chain variable region including the amino acid sequences of SEQ ID NOs: 37 to 39, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 40 to 42; (e) a light chain variable region including the amino acid sequences of SEQ ID NOs: 43 to 45, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 46 to 48; (f) a light chain variable region including the amino acid sequences of SEQ ID NOs: 49 to 51, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 52 to 54; (g) a light chain variable region including the amino acid sequences of SEQ ID NOs: 55 to 57, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 58 to 60; and (h) a light chain variable region including the amino acid sequences of SEQ ID NOs: 61 to 63, and a heavy chain variable region including the amino acid sequences of SEQ ID NOs: 64 to 66.