Internalizing human monoclonal antibodies targeting prostate and other cancer cells
In various embodiments various cancer specific antibodies and immunoconjugates are provided. In certain embodiments the antibodies specifically bind and are internalized into a prostate cancer cell, where the antibodies specifically binds cells that express or overexpress a CD46, and where the antibodies specifically bind sushi domain 1 of said CD46 (CD46 CPP1).
1. An isolated antibody that specifically binds and is internalized into a prostate cancer cell, wherein:
said antibody is an antibody that specifically binds cells that express or overexpress a CD46, wherein said antibody specifically binds sushi domain 1 of said CD46; and
said antibody comprises VH CDR1, VH CDR2, and VH CDR3 of the 2B10 antibody and VL CDR1, VL CDR2, and VL CDR3 of the 2B10 antibody.
2. The antibody of claim 1 , wherein said cells that express or overexpress a CD46 are prostate cancer cells.
3. The antibody of claim 1 , wherein said antibody bind cells of a cell line selected from the group consisting of DU145 cells, PC3 cells, and LnCaP cells.
4. The antibody of claim 1 , wherein said antibody is a substantially intact immunoglobulin.
5. The antibody of claim 4 , wherein said antibody comprises an IgA, IgE, or IgG isotype.
6. The antibody of claim 1 , wherein said antibody is an antibody fragment selected from the group consisting of Fv, Fab, (Fab′) 2 , (Fab′) 3 , IgGΔCH2, and a minibody.
7. The antibody of claim 1 , wherein said antibody is a single chain antibody.
8. The antibody of claim 7 , wherein the VL region of said antibody is attached to the VH region of said antibody by an amino acid linker ranging in length from about 3 amino acids up to about 15 amino acids.
9. The antibody of claim 7 , wherein the VL region of said antibody is attached to the VH region of said antibody by an amino acid linker selected from the group consisting of GGGGS GGGGS GGGGS (SEQ ID NO:2), GGGGS GGGGS (SEQ ID NO:3), GGGGS (SEQ ID NO:4), GS GGGGS GGGGS GGS GGGGS (SEQ ID NO:5), SGGGGS (SEQ ID NO:6), GGGS (SEQ ID NO:7), VPGV (SEQ ID NO:8), VPGVG (SEQ ID NO:9), GVPGVG (SEQ ID NO:10), GVG VP GVG (SEQ ID NO:11), VP GVG VP GVG (SEQ ID NO:12), GGSSRSS (SEQ ID NO:13), and GGSSRSSSSGGGGSGGGG (SEQ ID NO:14).
10. The antibody of claim 1 , wherein said antibody comprises the variable light (VL) chain of the 2B10 antibody and the variable heavy (VH) chain of the 2B10 antibody.
11. The antibody of claim 1 , wherein said antibody is a human scFv.
12. The antibody of claim 1 , wherein said antibody is a human 2B10 IgG.
13. An immunoconjugate comprising an antibody of claim 1 attached to an effector wherein said effector is selected from the group consisting of a second antibody, a detectable label, a cytotoxin or cytostatic agent, a liposome containing a drug, a radionuclide, a drug, a prodrug, a viral particle, a cytokine, and a chelate.
14. A pharmaceutical formulation said formulation comprising:
a pharmaceutically acceptable excipient and an antibody of claim 1 or a pharmaceutically acceptable excipient and a immunoconjugate of claim 13 .
15. The immunoconjugate of claim 13 , wherein said antibody comprises the variable light (VL) chain of the 2B10 antibody and the variable heavy (VH) chain of the 2B10 antibody.
16. The immunoconjugate of claim 13 , wherein said antibody is a substantially intact immunoglobulin.
17. The immunoconjugate of claim 15 , wherein said antibody is a substantially intact immunoglobulin.
18. The immunoconjugate of claim 13 , wherein said antibody is a single chain antibody.
19. The immunoconjugate of claim 13 , wherein said antibody is the 2B10 antibody.
20. The immunoconjugate of claim 13 , wherein said effector is an anticancer drug.
21. The antibody of claim 1 , wherein said antibody is the 2B10 antibody.
22. The antibody of claim 10 , wherein said antibody is a substantially intact immunoglobulin.
23. The antibody of claim 22 , wherein said antibody comprises an IgA, IgE, or IgG isotype.
24. The antibody of claim 10 , wherein said antibody is an antibody fragment selected from the group consisting of Fv, Fab, (Fab′) 2 , (Fab′) 3 , IgGΔCH2, and a minibody.
25. The antibody of claim 10 , wherein said antibody is a single chain antibody.
26. The antibody of claim 25 , wherein the VL region of said antibody is attached to the VH region of said antibody by an amino acid linker ranging in length from about 3 amino acids up to about 15 amino acids.
27. The antibody of claim 26 , wherein the VL region of said antibody is attached to the VH region of said antibody by an amino acid linker selected from the group consisting of GGGGS GGGGS GGGGS (SEQ ID NO:2), GGGGS GGGGS (SEQ ID NO:3), GGGGS (SEQ ID NO:4), GS GGGGS GGGGS GGS GGGGS (SEQ ID NO:5), SGGGGS (SEQ ID NO:6), GGGS (SEQ ID NO:7), VPGV (SEQ ID NO:8), VPGVG (SEQ ID NO:9), GVPGVG (SEQ ID NO:10), GVG VP GVG (SEQ ID NO:11), VP GVG VP GVG (SEQ ID NO:12), GGSSRSS (SEQ ID NO:13), and GGSSRSSSSGGGGSGGGG (SEQ ID NO:14).
28. A pharmaceutical formulation comprising:
an antibody comprising the variable light (VL) chain of the 2B10 antibody and the variable heavy (VH) chain of the 2B10 antibody; and
a pharmaceutically acceptable excipient.
29. A pharmaceutical formulation said formulation comprising:
2B10 antibody; and
a pharmaceutically acceptable excipient.
30. A pharmaceutical formulation said formulation comprising:
an immunoconjugate comprising the 2B10 antibody attached to an effector wherein said effector is selected from the group consisting of a second antibody, a detectable label, a cytotoxin or cytostatic agent, a liposome containing a drug, a radionuclide, a drug, a prodrug, a viral particle, a cytokine, and a chelate; and
a pharmaceutically acceptable excipient.