Agonistic antibody to CD27
The invention relates to a binding compound, which binds the same epitope of human CD27 as monoclonal antibody hCD27.15, produced by hybridoma hCD27.15 which was deposited with the ATCC in on Jun. 2, 2010 under number PTA-11008. In particular the invention relates to such a binding compound of claim 1 which may comprise: an antibody heavy chain variable region which may comprise at least one CDR selected from the group consisting of SEQ ID NOs: 5, 6 and 7, or a variant of any of said sequences; and/or an antibody light chain variable region which may comprise at least one CDR selected from the group consisting of SEQ ID NOs: 8, 9 and 10, or a variant of any of said sequences.
1. An antibody or antigen-binding fragment thereof, which binds to human CD27 comprising:
an antibody heavy chain variable region comprising the CDRs of SEQ ID NOs: 5, 6 and 7; and
an antibody light chain variable region comprising the CDRs of SEQ ID NOs: 8, 9 and 10.
2. The antibody or antigen-binding fragment thereof of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4.
3. The antibody or antigen-binding fragment thereof of claim 1 , which is monoclonal antibody hCD27.15 as produced by hybridoma hCD27.15 (deposit accession number PTA-11008).
4. The antibody or antigen-binding fragment thereof of claim 1 , which:
binds human CD27 with a K D of about 100 nM or lower; and
blocks binding of human CD27 to human CD70 with an IC 50 of about 10 nM or lower.
5. A human or humanized antibody or antigen-binding fragment thereof which competes for binding to human CD27 with an antibody or antigen-binding fragment thereof which binds to human CD27, said antibody or antigen-binding fragment thereof comprising:
an antibody heavy chain variable region comprising the CDRs of SEQ ID NOs: 5, 6 and 7; and an antibody light chain variable region comprising the CDRs of SEQ ID NOs: 8, 9 and 10,
wherein said human or humanized antibody or antigen-binding fragment thereof is able to activate human CD27 (hCD27) signaling more effectively than soluble human CD70 fused to the C-terminus of the dimerization domain of IgG1 as measured by NFκB activation in an in vitro assay, wherein said human or humanized antibody is present at a concentration of 10 μg/mL, or wherein said antigen-binding fragment is present at a molar concentration equivalent to 10 μg/mL of said human or humanized antibody, wherein said soluble human CD70 fused to the C-terminus of the dimerization domain of IgG1 is present at a concentration of 2 μg/mL, and wherein hCD27 is expressed in HEK293 cells transient transfected with a hCD27 encoding nucleic acid.
6. The antibody or antigen-binding fragment thereof of claim 1 , which is
a chimeric antibody or an antigen-binding fragment thereof; or
an antibody fragment selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , bispecific mAb and a diabody.
7. A polynucleotide encoding the antibody or antigen-binding fragment thereof as claimed in claim 1 .
8. The polynucleotide of claim 7 , comprising SEQ ID NOs 1 and 2, which encode the heavy and light chain of hCD27.15.
9. An expression vector comprising the polynucleotide of claim 7 or 8 .
10. A host cell comprising the expression vector of claim 9 .
11. A host cell comprising the polynucleotide of claim 7 or 8 .
12. A method of producing an antibody or antigen-binding fragment thereof, which method comprises:
a) culturing a host cell comprising an expression vector that comprises a polynucleotide encoding the antibody or antigen-binding fragment thereof of claim 1 under the control of suitable regulatory sequences in culture medium under conditions wherein the polynucleotide is expressed, thereby producing polypeptides comprising the light and heavy chain variable regions; and
b) recovering the polypeptides from the host cell or culture medium.
13. A composition comprising the antibody or antigen-binding fragment thereof of claim 1 in combination with a pharmaceutically acceptable carrier or diluent.
14. The composition of claim 13 , further comprising an anti-cancer drug.
15. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof exhibits agonist activity on CD27.
16. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof is able to activate human CD27 (hCD27) signaling more effectively than soluble human CD70 fused to the C-terminus of the dimerization domain of IgG1 as measured by NFκB activation in an in vitro assay, wherein said antibody is present at a concentration of 10 μg/mL, or wherein said antigen-binding fragment is present at a molar concentration equivalent to 10 μg/mL of said antibody, wherein said soluble human CD70 fused to the C-terminus of the dimerization domain of IgG1 is present at a concentration of 2 μg/mL, and wherein hCD27 is expressed in HEK293 cells transient transfected with a hCD27 encoding nucleic acid.
17. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof binds human CD27 with at least a K D of 10 −6 M.
18. The antibody or antigen binding fragment thereof of claim 5 , which has one or more of the following characteristics:
binds human CD27 with a K D of about 100 nM or lower;
binds to human CD27 with about the same K D as an antibody having a heavy chain comprising the amino acid sequence of SEQ ID NO: 3 and a light chain comprising the amino acid sequence of SEQ ID NO: 4; and/or
blocks binding of human CD27 to human CD70 with an IC 50 of about 10 nM or lower.
19. A human or humanized version of the antibody or antigen-binding fragment thereof of claim 1 .