TGF-β1 specific antibodies and methods and uses thereof

A method of inhibiting or reducing recurrence or metastasis of cancer in a mammal wherein TGF-β1 is expressed in the cancer or in a tumor of the cancer which comprises administering to said mammal an effective amount of an antibody molecule or fragment thereof which recognizes human and mouse transforming growth factor beta 1 (TGF-β1) and does not react with TGF-β2 and does not react with TGF-β3, wherein the antibody or fragment neutralizes activity of TGF-β1, and is an antibody or fragment comprising a heavy chain variable region comprising CDR domain sequences CDR1 GYTFTNYW (SEQ ID NO:

• 11), CDR2 IYPGNSDT (SEQ ID NO:
• 12) and CDR3 EDSRSLYYNGWDYFDY (SEQ ID NO:
• 5) or comprising CDR domain sequences CDR1 GYTFTNYWMH (SEQ ID NO:
• 3), CDR2 TIYPGNSDTN (SEQ ID NO:
• 4) and CDR3 EDSRSLYYNGWDYFDY (SEQ ID NO:
• 5), and a light chain variable region comprising CDR domain sequences CDR1 ESVDNYGISF (SEQ ID NO:
• 6), CDR2 YAAS (SEQ ID NO:
• 7) and CDR3 QQSKEVPRT (SEQ ID NO:
• 8).

A method for stimulating or enhancing an anti-tumor immune response to a cancer vaccine or cancer antigen in a mammal, wherein TGF-31 is expressed in the tumor, which comprises administering to said mammal an effective amount of an antibody molecule or fragment thereof which recognizes human and mouse transforming growth factor beta 1 (TGF-β1) and does not react with TGF-β2 and does not react with TGF-β3, wherein the antibody or fragment neutralizes activity of TGF-β1, and is an antibody or fragment comprising a heavy chain variable region comprising CDR domain sequences CDR1 GYTFTNYW (SEQ ID NO:

• 11), CDR2 IYPGNSDT (SEQ ID NO:
• 12) and CDR3 EDSRSLYYNGWDYFDY (SEQ ID NO:
• 5) or comprising CDR domain sequences CDR1 GYTFTNYWMH (SEQ ID NO:
• 3), CDR2 TIYPGNSDTN (SEQ ID NO:
• 4) and CDR3 EDSRSLYYNGWDYFDY (SEQ ID NO:
• 5), and a light chain variable region comprising CDR domain sequences CDR1 ESVDNYGISF (SEQ NO:
• 6), CDR2 YAAS (SEQ ID NO:
• 7) and CDR3 QQSKEVPRT (SEQ ID NO:
• 8).

A method for enhancing the anti-cancer immune response in a mammal comprising administering to said mammal an effective amount of an antibody molecule or fragment thereof which recognizes human and mouse transforming growth factor beta 1 (TGF-β1) and does not react with TGF-β2 and does not react with TGF-β3, wherein the antibody or fragment is an antibody or fragment comprising a heavy chain variable region comprising CDR domain sequences CDR1 GYTFTNYW (SEQ ID NO:

• 11), CDR2 IYPGNSDT (SEQ ID NO:
• 12) and CDR3 EDSRSLYYNGWDYFDY (SEQ ID NO:
• 5) or comprising CDR domain sequences CDR1 GYTFTNYWMH (SEQ ID NO:
• 3), CDR2 TIYPGNSDTN (SEQ ID NO:
• 4) and CDR3 EDSRSLYYNGWDYFDY (SEQ ID NO:
• 5), and a light chain variable region comprising CDR domain sequences CDR1 ESVDNYGISF (SEQ ID NO:
• 6), CDR2 YAAS (SEQ ID NO:
• 7) and CDR3 QQSKEVPRT (SEQ ID NO:
• 8), and further administering an immune modulator selected from indoleamine-2,3-dioxygenase (IDO), tryptophan-2,3-dioxygenase (TDO), α-galactosyl ceramide or α-galactosyl ceramide analog threitolceramide (IMM47), toll-like receptor (TLR) ligands, inducible T-cell co-stimulator (iCOS), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD1), PD1 ligand, OX40(CD134), OX40 ligand, lymphocyte-activation gene 3 (Lag3), glucocorticoid-induced TNFR-related protein (GITR), GITR ligand, interleukins and tumor necrosis factor (TNF).