TGF-β1 specific antibodies and methods and uses thereof
Specific binding members, particularly antibodies and fragments thereof, which bind to transforming growth factor beta 1 (TGF-β1) are provided, particularly recognizing human and mouse TGF-β1 and not recognizing or binding TGF-β2 or TGF-β3. Particular antibodies are provided which specifically recognize and neutralize TGF-β1. These antibodies are useful in the diagnosis and treatment of conditions associated with activated or elevated TGF-β1, including cancer, and for modulating immune cells and immune response, including immune response to cancer or cancer antigens. The anti-TGF-β1 antibodies, variable regions or CDR domain sequences thereof, and fragments thereof may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof. Antibodies of this type are exemplified by the novel antibodies hereof, including antibody 13A1, whose sequences are provided herein.
1. An isolated nucleic acid which comprises a sequence encoding an antibody 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).
2. The nucleic acid of claim 1 which encodes an antibody or antibody 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) 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).
3. The nucleic acid of claim 1 which encodes an antibody or antibody fragment comprising a heavy chain variable region 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).
4. The nucleic acid of claim 1 which encodes an antibody or antibody fragment comprising a heavy chain variable region amino acid sequence selected from the amino acid sequence SEQ ID NO: 1, or variants thereof having at least 90% amino acid identity to SEQ ID NO:1.
5. The nucleic acid of claim 1 or 4 which encodes an antibody or antibody fragment comprising a light chain variable region comprising an amino acid sequence selected from the amino acid sequence as set out in SEQ ID NO: 2, or variants thereof having at least 90% amino acid identity to SEQ ID NO:2.
6. The nucleic acid of claim 1 which comprises DNA.
7. A recombinant DNA molecule comprising the sequence of claim 1 .
8. The recombinant DNA molecule of claim 7 , wherein said sequence is operatively linked to an expression control sequence.
9. A unicellular host transformed with a recombinant DNA molecule of claim 7 or 8 .
10. A vector which comprises the recombinant DNA molecule of claim 7 or 8 .
11. An isolated host vector system for the production of an antibody or fragment thereof which comprises the vector of claim 10 in a suitable host cell.
12. A method of preparing an antibody 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, which comprises expressing the nucleic add of claim 1 or any one of claims 2 - 4 under conditions to bring about expression of said antibody or fragment, and recovering the antibody or fragment.