CD37-binding molecules and immunoconjugates thereof
Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to CD37 are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.
1. An antibody produced by the hybridoma of ATCC Deposit Designation PTA-10664 or an antigen-binding fragment thereof.
2. An isolated antibody or antigen binding fragment thereof that specifically binds to CD37, wherein said antibody, or antigen binding fragment comprises the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 polypeptide sequences of
SEQ ID NOs: 4, 5, and 6 and SEQ ID NOs: 28, 29, and 30 respectively.
3. An isolated cell producing the antibody or antigen binding fragment thereof of claim 2 .
4. A method of making an anti-CD37 antibody or antigen-binding fragment thereof comprising (a) culturing the cell of claim 3 ; and (b) isolating said antibody, or antigen-binding fragment thereof from said cultured cell.
5. An immunoconjugate having the formula (A)-(L)-(C), wherein:
(A) is the antibody or antigen binding fragment of claim 2 ;
(L) is a linker; and
(C) is a cytotoxic agent; and
wherein said linker (L) links (A) to (C).
6. The immunoconjugate of claim 5 comprising 3-4 (C) per (A).
7. The immunoconjugate of claim 5 , wherein said linker is selected from the group consisting: N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP); N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) or N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB); N-succinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (SMCC); N-sulfosuccinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (sulfoSMCC); N-succinimidyl-4-(iodoacetyl)-aminobenzoate (SIAB); and N-succinimidyl-[(N-maleimidopropionamido)-tetraethyleneglycol]ester (NHS-PEG4-maleimide).
8. The immunoconjugate of claim 5 , wherein said cytotoxic agent is selected from the group consisting of a maytansinoid, maytansinoid analog, doxorubicin, a modified doxorubicin, benzodiazepine, taxoid, CC-1065, CC-1065 analog, duocarmycin, duocarmycin analog, calicheamicin, dolastatin, dolastatin analog, aristatin, tomaymycin derivative, and leptomycin derivative or a prodrug of the agent.
9. The immunoconjugate of claim 8 , wherein said cytotoxic agent is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine (DM1) or N(2′)-deacetyl-N2-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4).
10. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 2 and a pharmaceutically acceptable carrier.
11. A pharmaceutical composition comprising the immunoconjugates of claim 5 , wherein the immunoconjugates have an average of about 3 to about 4 (C) per (A).
12. A diagnostic reagent comprising the antibody or antigen binding fragment thereof of claim 2 .
13. A kit comprising the antibody or antigen binding fragment thereof of claim 2 .
14. The immunoconjugate of claim 5 , wherein the antibody comprises the polypeptide sequences of SEQ ID NO:57 and SEQ ID NO:74.
15. The antibody or antigen binding fragment of claim 2 , wherein the antibody or antigen binding fragment comprises the polypeptide sequences of SEQ ID NO:57 and SEQ ID NO:74.
16. The immunoconjugate of claim 5 , wherein said linker is SMCC.
17. The immunoconjugate of claim 16 , wherein said cytotoxic agent is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine (DM1).
18. The immunoconjugate of claim 14 , wherein said linker is SMCC.
19. The immunoconjugate of claim 14 , wherein said cytotoxic agent is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine (DM1).
20. The immunoconjugate of claim 18 , wherein said cytotoxic agent is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine (DM1).
21. An immunoconjugate having the formula (A)-(L)-(C), wherein:
(A) is the antibody or antigen binding fragment of claim 15 ;
(L) is a linker; and
(C) is a cytotoxic agent; and
wherein said linker (L) links (A) to (C).
22. A pharmaceutical composition comprising the antibody or antigen binding fragment of claim 15 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising the immunoconjugate of claim 17 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising the immunoconjugate of claim 20 and a pharmaceutically acceptable carrier.
25. A pharmaceutical composition comprising the immunoconjugates of claim 17 , wherein the immunoconjugates have an average of about 3 to about 4 (C) per (A).
26. A pharmaceutical composition comprising the immunoconjugates of claim 20 , wherein the immunoconjugates have an average of about 3 to about 4 (C) per (A).