METHODS AND COMPOSITIONS RELATED TO ANTIBODY FRAGMENTS THAT BIND TO TUMOR-ASSOCIATED GLYCOPROTEIN 72 (TAG-72)
Antibodies recognizing TAG-72 provide a novel approach for the imaging, detection, and treatment of cancer. These methods are made possible by using antibody fragments that bind specifically to the sialyl-Tn surface adhesin of TAG-72. Antibody fragment derivatives are advantageously useful over other antibody and antibody fragments known in the art because they are easy to express in large quantities, can penetrate tissues easily and lack the constant domains that promote often unwanted and usually superfluous effector functions.
1 . An antibody fragment which specifically binds tumor-associated glycoprotein 72 (TAG-72), wherein the antibody fragment comprises an amino acid sequence with 98% or more identity to SEQ ID NO: 13, 33, 35, 37, 39, 41, 43, or 45, wherein said antibody fragment comprises complementarity determining regions (CDRs), wherein said CDRs comprise amino acid residues 53-57, 72-88, 22-126, 166-182, 198-204, and 237-245 of SEQ ID NO: 13; residues 76-80, 95-111, 144-149, 189-205, 221-227, and 260-268 of SEQ ID NO: 33; residues 76-80, 95-111, 144-149, 209-225, 241-247, and 280-288 of SEQ ID NO: 35; residues 76-80, 95-111, 144-149, 204-220, 236-242, and 275-283 of SEQ ID NO: 37; residues 76-80, 95-111, 144-149, 199-215, 231-237, and 270-278 of SEQ ID NO: 39; residues 76-80, 95-111, 144-149, 188-204, 220-226, and 259-267 of SEQ ID NO: 41; residues 76-80, 95-111, 144-149, 188-204, 220-226, and 259-267 of SEQ ID NO: 43; and residues 76-80, 95-111, 144-149, 189-205, 221-227, and 260-268 of SEQ ID NO: 45.
2 . (canceled)
3 . The antibody fragment of claim 1 , wherein the fragment has increased tissue penetrance compared to full-length antibodies (IgG) and fragment antigen binding (Fab) domains.
4 . (canceled)
5 . The antibody fragment of claim 1 , wherein the antibody fragment comprises a heavy chain variable region comprising SEQ ID NO: 10, and a light chain variable region comprising SEQ ID NO: 11.
6 . The antibody fragment of claim 1 , wherein said antibody fragment has an antigen binding affinity for sialyl-Tn which is at least 25% that of 3E8.
7 - 12 . (canceled)
13 . The antibody fragment of claim 1 , wherein the antibody fragment is a diabody, a tribody, a tetrabody, or a combination of any of those.
14 . A composition comprising the antibody fragment of claim 1 and a pharmaceutically acceptable carrier.
15 . (canceled)
16 . The composition of claim 14 , wherein said antibody fragment is, directly or indirectly, associated with or linked to an effector moiety having therapeutic activity, and the composition is suitable for the treatment of cancer.
17 . The composition of claim 16 , wherein said effector moiety is a radionuclide, therapeutic enzyme, anti-cancer drug, cytokine, cytotoxin, or anti-proliferative agent.
18 . (canceled)
19 . The composition of claim 14 , wherein said antibody fragment is, directly or indirectly, associated with or linked to a detectable label, and the composition is suitable for detection of cancer.
20 . The composition of claim 19 , wherein the detectable label is a radionuclide or an enzyme.
21 - 38 . (canceled)