Anti-CD40 antibodies
The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccines and antigen delivery vectors, to delivery antigens to antigen presenting cells. In one embodiment, the vector is an anti-CD40 antibody, or fragments thereof, and one or more antigenic peptides linked to the anti-CD40 antibody or fragments thereof, including humanized antibodies.
1. An antibody or an antigen binding fragment thereof, that binds to CD40, comprising light chain complementarity determining regions 1, 2, and 3 corresponding to SEQ ID NO: 41, SEQ ID NO: 42 and SEQ ID NO: 43, respectively and heavy chain complementarity determining regions 1, 2, and 3 corresponding to SEQ ID NO: 44, SEQ ID NO: 45 and SEQ ID NO: 46, respectively.
2. The antibody of claim 1 , further comprising a heavy chain constant region, wherein the heavy chain constant region comprises a gamma-1, gamma-2, gamma-3, or gamma-4 human heavy chain constant region or a variant of the human heavy chain constant region.
3. The antibody of claim 1 , wherein the antibody comprises a) at least one antibody light chain variable region of SEQ ID NO:2; and b) at least one antibody heavy chain variable region of SEQ ID NO:1.
4. The antibody of claim 1 , further comprising a light chain constant region, wherein the light chain constant region comprises a lambda or a kappa human light chain constant region.
5. The antibody of claim 1 , wherein the binding fragment is selected from group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , and a diabody.
6. The antibody of claim 1 , wherein the antibody, or antigen binding fragment thereof, comprises the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of SEQ ID NO: 1.
7. The antibody of claim 1 , wherein the antibody alone is capable of causing dendritic cells to secrete at least one of IL-6, MIP-1a, IL-12p40 or TNFalpha without prior activation of the dendritic cells.
8. The antibody of claim 1 , wherein the antibody is capable of causing dendritic cells activated with GM-CSF and Interferon alpha to secrete at least one of IL-6, MIP-1a, IP-10, IL-10 or IL-12p40.
9. A composition comprising an antibody or an antigen binding fragment thereof, in combination with a pharmaceutically acceptable carrier or diluent, wherein the antibody is the antibody of claim 1 .
10. A recombinant antibody or an antigen binding fragment thereof that binds to CD40, wherein the antibody alone is capable of causing dendritic cells to secrete at least one of IL-6, MIP-1a, IL-12p40 or TNFalpha without prior activation of the dendritic cells, wherein the antibody comprises light chain complementarity determining regions 1, 2, and 3 corresponding to SEQ ID NO: 41, SEQ ID NO: 42 and SEQ ID NO: 43, respectively, and heavy chain complementarity determining regions 1, 2, and 3 corresponding to SEQ ID NO: 44, SEQ ID NO: 45 and SEQ ID NO: 46, respectively.
11. The antibody of claim 10 , wherein the antibody comprises the heavy chain variable region of SEQ ID NO: 1 and the light chain variable region of SEQ ID NO: 2.
12. The antibody of claim 10 , wherein the antibody is produced by a hybridoma selected from anti-CD40 12E12.3F3 (ATCC Accession No. PTA-9854).
13. The antibody of claim 10 , wherein the antibody is humanized.
14. A recombinant antibody or an antigen binding fragment thereof that binds to CD40, wherein the antibody alone is capable of causing B cell proliferation of at least 10% of the B cells, wherein the antibody comprises light chain complementarity determining regions 1, 2, and 3 corresponding to SEQ ID NO: 41, SEQ ID NO: 42 and SEQ ID NO: 43, respectively, and heavy chain complementarity determining regions 1, 2, and 3 corresponding to SEQ ID NO: 44, SEQ ID NO: 45 and SEQ ID NO: 46, respectively.
15. The antibody of claim 14 , wherein the percentage of B cells that proliferate is at least 15%, 20%, 25%, 28%, 30% or 35%.
16. The antibody of claim 14 , wherein the antibody comprises the heavy chain variable region of SEQ ID NO: 1 and the light chain variable region of SEQ ID NO:2.
17. The antibody of claim 14 , wherein the antibody is produced by a hybridoma selected from anti-CD40 12E12.3F3.
18. The antibody of claim 14 , wherein the antibody alone is capable of causing dendritic cells to secrete at least one of IL-6, MIP-1a, IL-12p40 or TNFalpha without prior activation of the dendritic cells.
19. The antibody of claim 14 , wherein the antibody is capable of causing dendritic cells activated with GM-CSF and Interferon alpha to secrete at least one of IL-6, MIP-1a, IP-10, IL-10 or IL-12p40.
20. The antibody of claim 14 , wherein the antibody is humanized.