Anti-MUC-1 single chain antibodies for tumor targeting

A nucleic acid that encodes an antibody that specifically binds MUC-1, said nucleic acid comprising a nucleotide sequence encoding an amino acid sequence selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a B5 variable light domain (SEQ ID NO:10), an E1 variable light domain (SEQ ID NO:12), a B9 variable light domain (SEQ ID NO:14);

• a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), a C4 variable heavy domain (SEQ ID NO:7), a B5 variable heavy domain (SEQ ID NO:9), an E1 variable heavy domain (SEQ ID NO:11), and a B9 variable heavy domain (SEQ ID NO:13)..

A chimeric molecule comprising an antibody attached to an effector, wherein:

• said antibody is an antibody that specifically binds MUC-1, said antibody comprising a domain comprising an amino acid sequence of a polypeptide selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a B5 variable light domain (SEQ ID NO:10), an E1 variable light domain (SEQ ID NO:12), a B9 variable light domain (SEQ ID NO:14), a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), a C4 variable heavy domain (SEQ ID NO:7), a B5 variable heavy domain (SEQ ID NO:9), an E1 variable heavy domain (SEQ ID NO:11), and a B9 variable heavy domain (SEQ ID NO:13).;
• and
• said effector is selected from the group consisting of an epitope tag, a second antibody, a label, a cytotoxin, a liposome, a radionuclide, a drug, a prodrug, a liposome, and a chelate.

A method of detecting a cell bearing a MUC-1 antigen, said method comprising:

• contacting a cell bearing a MUC-1 antigen with a chimeric molecule comprising an anti-MUC-1 antibody attached to a detectable label;
• and
• detecting said detectable label.

A method of inhibiting growth or proliferation of a cell bearing a MUC-1 antigen, said method comprising:

• contacting said cell bearing a MUC-1 antigen with a chimeric molecule comprising an anti-MUC-1 antibody attached to an effector selected from the group consisting of a cytotoxin, a radionuclide, a liposome comprising an anti-cancer drug, a prodrug, and an anti-cancer drug;
• wherein said antibody comprises a domain comprising the amino acid sequence of a polypeptide selected from the group consisting of consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a B5 variable light domain (SEQ ID NO:10), an E1 variable light domain (SEQ ID NO:12), a B9 variable light domain (SEQ ID NO:14), a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), a C4 variable heavy domain (SEQ ID NO:7), a B5 variable heavy domain (SEQ ID NO:9), an E1 variable heavy domain (SEQ ID NO:11), and a B9 variable heavy domain (SEQ ID NO:13).

An antibody that specifically binds MUC-1 at an epitope specifically bound by a single-chain antibody comprising polypeptide selected from the group consisting of 12E (SEQ ID NO:15), 3D(SEQ ID NO:16), A5 (SEQ ID NO:17), C4 (SEQ ID NO:18), B5 (SEQ ID NO:19), E1 (SEQ ID NO:20), and B9 (SEQ ID NO:21).

An antibody that specifically binds MUC-1 at an epitope specifically bound by a single-chain antibody said antibody comprising the amino acid sequence of a variable heavy chain and a variable light chain of an antibody selected from the group consisting of 12E (SEQ ID NO:15), 3D(SEQ ID NO:16), A5 (SEQ ID NO:17), C4 (SEQ ID NO:18), B5 (SEQ ID NO:19), E1 (SEQ ID NO:20), and B9 (SEQ ID NO:21), or conservative substitutions thereto.