Antibodies that bind to cancer-associated antigen CD46 and methods of use thereof
Provided herein is disclosure about the development and characterization of an antibody (mPA7) which binds to antigen CD46 which is present on a variety of human cancers from ovary, breast, lung, prostate, colon, kidney, and pancreas. Methods of diagnosing and treating various cancers by using antibodies such as mPA7 directed against this antigen are also disclosed.
1. An antibody mPA7 produced by a host cell with a deposit number of ATCC No. PTA-3706.
2. A chimeric antibody comprising the variable regions of a light chain and a heavy chain of the antibody mPA7 of claim 1 and constant regions of a light chain and a heavy chain of a human antibody, wherein said antibody has or retains the binding specificity of said antibody mPA7.
3. A humanized antibody comprising each of three CDRs from the light chain of the antibody mPA7 of claim 1 and each of three CDRs from the heavy chain of the antibody mPA7 of claim 1 , wherein said antibody has or retains the binding specificity of said antibody mPA7.
4. A fragment of the mPA7 antibody of claim 1 , wherein the fragment comprises the variable region of a heavy chain and the variable region of a light chain of said antibody mPA7, and wherein said fragment has or retains the binding specificity of said antibody mPA7.
5. A fragment of the mPA7 antibody of claim 1 , wherein said fragment has or retains the binding specificity of said antibody mPA7.
6. A heavy chain of the antibody mPA7 of claim 1 .
7. A light chain of the antibody mPA7 of claim 1 .
8. A light chain comprising the three CDRs of a light chain of the antibody mPA7 of claim 1 .
9. A heavy chain comprising the three CDRs of a heavy chain of the antibody mPA7 of claim 1 .
10. A single-chain Fv comprising the variable regions of the light and heavy chains of the antibody mPA7 of claim 1 , wherein said single-chain Fv has or retains the binding specificity of said antibody mPA7.
11. A kit comprising an antibody according to any one of claims 1 , 2 , and 3 .
12. A composition comprising the antibody of claim 2 , wherein the antibody is linked to a therapeutic agent.
13. A pharmaceutical composition comprising the antibody of claim 2 and a pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising the antibody of claim 2 and a pharmaceutically acceptable excipient, wherein the antibody is linked to a therapeutic agent.
15. A fragment of a chimeric antibody according to claim 2 , wherein said fragment has or retains the binding specificity of said antibody mPA7.
16. A composition comprising the antibody of claim 3 , wherein the antibody is linked to a therapeutic agent.
17. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable excipient.
18. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable excipient, wherein the antibody is linked to a therapeutic agent.
19. A fragment of a humanized antibody according to claim 11 , wherein said fragment has or retains the binding specificity of said antibody mPA7.
20. A method of generating the antibody of claim 2 , or 3 comprising expressing one or more polynucleotides encoding the antibody of claim 2 or 3 , respectively, and purifying the antibody, thereby generating the antibody.
21. The fragment of claim 4 , wherein the fragment is a Fab.
22. The fragment of claim 4 , wherein the fragment is a Fab′.
23. The fragment of claim 4 , wherein the fragment is a F(ab′) 2 .
24. The fragment of claim 4 , wherein the fragment is a Fv.
25. A method of generating a fragment according to claim 4 comprising expressing one or more polynucleotides encoding the fragment, and purifying the fragment, thereby generating the fragment.
26. A composition comprising the fragment of any one of claims 4 – 19 , wherein the fragment is linked to a therapeutic agent.
27. A kit comprising the fragment according to any one of claims 4 – 19 .
28. A host cell line (ATCC No. PTA-3706).
29. A method of generating antibody mPA7 comprising culturing a host cell line according to claim 28 under conditions that allow production of antibody mPA7, and purifying the antibody, thereby generating antibody mPA7.