TES7 and antibodies that bind thereto
The invention provides the identification and characterization of disease and cancer-associated antigen, TES7. The invention also provides a family of monoclonal antibodies that bind to antigen TES7, methods of diagnosing and treating various human cancers and diseases that express TES7.
1. A substantially purified immunoglobulin polypeptide or an antigen-binding fragment thereof, that specifically binds to 4Ig form of B7H3 expressed on a cancer cell, but does not specifically bind to 2Ig B7H3 and is unable to cross-link 4Ig-B7H3.
2. The purified immunoglobulin polypeptide or antigen binding fragment of claim 1 , wherein said cancer cell is selected from the group consisting of a cancer cell from: an adrenal gland tumor, an AIDS-associated cancer, an alveolar soft part sarcoma, an astrocytic tumor, a bladder cancer, a bone cancer, a brain or spinal cord cancer, a metastatic brain tumor, a breast cancer, a carotid body tumor, a cervical cancer, a chondrosarcoma, a dhordoma, a chromophobe renal cell carcinoma, a clear cell carcinoma, a colon cancer, a colorectal cancer, a cutaneous benign fibrous histiocytoma histiocytomas, a desmoplastic small round cell tumor, an ependymoma, a Ewing's tumor, an extraskeletal myxoid chondrosarcoma, a fibrogenesis imperfecta ossium, a fibrous dysplasia of the bone, a gallbladder or bile duct cancer, a gestational trophoblastic disease, a germ cell tumor, a head and neck cancer, an islet cell tumor, a Kaposi's Sarcoma, a kidney cancer, a leukemia, a lipoma/benign lipomatous tumor, a liposarcoma/malignant lipomatous tumor, a liver cancer, a lymphoma, a lung cancer, a medulloblastoma, a melanoma, a meningioma, a multiple endocrine neoplasia, a multiple myeloma, a myelodysplastic syndrome cell, a neuroblastoma, a neuroendocrine tumor, an ovarian cancer, a pancreatic cancer, a papillary thyroid carcinoma, a parathyroid tumor, a pediatric cancer cell, a peripheral nerve sheath tumor, a phaeochromocytoma, a pituitary tumor, a prostate cancer, a posterious unveal melanoma, a rare hematologic disorder, a renal metastatic cancer, a rhabdoid tumor, a rhabdomysarcoma, a sarcoma, a skin cancer, a soft-tissue sarcoma, a squamous cell cancer, a stomach cancer, a synovial sarcoma, a testicular cancer, a thymic carcinoma, a thymoma, a thyroid metastatic cancer, and a uterine cancer.
3. A pharmaceutical composition comprising the purified immunoglobulin or antigen-binding fragment of claim 1 , together with a pharmaceutically acceptable carrier.
4. The pharmaceutical composition of claim 3 , wherein the composition comprises an additional therapeutic moiety.
5. A method for delivering a chemotherapeutic agent to a cancer cell comprising administering a composition comprising the polypeptide or antigen-binding fragment thereof of claim 1 associated with the chemotherapeutic agent, wherein said cancer cell is selected from the group consisting of a cancer cell from: an adrenal gland tumor, an AIDS-associated cancer, an alveolar soft part sarcoma, an astrocytic tumor, a bladder cancer, a bone cancer, a brain or spinal cord cancer, a metastatic brain tumor, a breast cancer, a carotid body tumor, a cervical cancer, a chondrosarcoma, a dhordoma, a chromophobe renal cell carcinoma, a clear cell carcinoma, a colon cancer, a colorectal cancer, a cutaneous benign fibrous histiocytoma, a desmoplastic small round cell tumor, an ependymoma, a Ewing's tumor, an extraskeletal myxoid chondrosarcoma, a fibrogenesis imperfecta ossium, a fibrous dysplasia of the bone, a gallbladder or bile duct cancer, a gestational trophoblastic disease, a germ cell tumor, a head and neck cancer, an islet cell tumor, a Kaposi's Sarcoma, a kidney cancer, a leukemia, a lipoma/benign lipomatous tumor, a liposarcoma/malignant lipomatous tumor, a liver cancer, a lymphoma, a lung cancer, a medulloblastoma, a melanoma, a meningioma, a multiple endocrine neoplasia, a multiple myeloma, a myelodysplastic syndrome cell, a neuroblastoma, a neuroendocrine tumor, an ovarian cancer, a pancreatic cancer, a papillary thyroid carcinoma, a parathyroid tumor, a pediatric cancer cell, a peripheral nerve sheath tumor, a phaeochromocytoma, a pituitary tumor, a prostate cancer, a posterious unveal melanoma, a rare hematologic disorder, a renal metastatic cancer, a rhabdoid tumor, a rhabdomysarcoma, a sarcoma, a skin cancer, a soft-tissue sarcoma, a squamous cell cancer, a stomach cancer, a synovial sarcoma, a testicular cancer, a thymic carcinoma, a thymoma, a thyroid metastatic cancer, and a uterine cancer.
6. The method of claim 5 , wherein the chemotherapeutic agent is administered to an individual.
7. The method of claim 5 , wherein the polypeptide is produced by the hybridoma having ATCC deposit number PTA-7093 or progeny thereof.
8. A method for detecting the presence or absence of a cancer cell in an individual comprising contacting cells from the individual with the polypeptide or antigen-binding fragment thereof of claim 1 , and detecting a complex of TES7 from the cells and the antibody, if any, wherein said cancer cell is selected from the group consisting of a cancer cell from: an adrenal gland tumor, an AIDS-associated cancer, an alveolar soft part sarcoma, an astrocytic tumor, a bladder cancer, a bone cancer, a brain or spinal cord cancer, a metastatic brain tumor, a breast cancer, a carotid body tumor, a cervical cancer, a chondrosarcoma, a dhordoma, a chromophobe renal cell carcinoma, a clear cell carcinoma, a colon cancer, a colorectal cancer, a cutaneous benign fibrous histiocytoma, a desmoplastic small round cell tumor, an ependymoma, a Ewing's tumor, an extraskeletal myxoid chondrosarcoma, a fibrogenesis imperfecta ossium, a fibrous dysplasia of the bone, a gallbladder or bile duct cancer, a gestational trophoblastic disease, a germ cell tumor, a head and neck cancer, an islet cell tumor, a Kaposi's Sarcoma, a kidney cancer, a leukemia, a lipoma/benign lipomatous tumor, a liposarcoma/malignant lipomatous tumor, a liver cancer, a lymphoma, a lung cancer, a medulloblastoma, a melanoma, a meningioma, a multiple endocrine neoplasia, a multiple myeloma, a myelodysplastic syndrome cell, a neuroblastoma, a neuroendocrine tumor, an ovarian cancer, a pancreatic cancer, a papillary thyroid carcinoma, a parathyroid tumor, a pediatric cancer cell, a peripheral nerve sheath tumor, a phaeochromocytoma, a pituitary tumor, a prostate cancer, a posterious unveal melanoma, a rare hematologic disorder, a renal metastatic cancer, a rhabdoid tumor a rhabdomysarcoma, a sarcoma, a skin cancer, a soft-tissue sarcoma, a squamous cell cancer, a stomach cancer, a synovial sarcoma, a testicular cancer, a thymic carcinoma, a thymoma, a thyroid metastatic cancer, and a uterine cancer.
9. An isolated antibody produced by the host cell line having ATCC deposit number PTA-7093 or progeny thereof.
10. An isolated antibody or an antigen-binding fragment thereof that specifically binds to 4Ig form of B7H3, the antibody comprising a heavy chain variable region comprising the three heavy chain CDRs and a light chain variable region comprising the three light chain CDRs from the antibody produced by the host cell line having ATCC deposit number PTA-7093.
11. The isolated antibody or the antigen-binding fragment of claim 10 , wherein the isolated antibody is a humanized antibody.
12. The isolated antibody or the antigen-binding fragment of claim 11 , wherein the heavy variable region of the humanized antibody comprises the amino acid sequence of SEQ ID NO:7 or 8.
13. The isolated antibody or the antigen-binding fragment of claim 11 , wherein the light variable region of the humanized antibody comprises the amino acid sequence of SEQ ID NO:3 or 4.
14. The isolated antibody or the antigen-binding fragment of claim 10 , wherein the isolated antibody is a chimeric antibody comprising the heavy and light variable regions from the antibody produced by the host cell line having ATCC deposit number PTA-7093.
15. The isolated antibody or the antigen-binding fragment of claim 14 , wherein the chimeric antibody comprises a heavy chain constant region from the heavy chain constant region from a human antibody, and a light chain constant region from the light chain constant region of a human antibody.
16. The isolated antibody or the antigen-binding fragment of claim 10 , wherein the antigen-binding fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′) 2 and a Fv.
17. An isolated antibody produced by the host cell line having ATCC deposit number PTA-8576 or progeny thereof.
18. An isolated antibody or an antigen-binding fragment thereof that specifically binds to 4Ig form of B7H3, the antibody comprising a heavy chain variable region comprising the three heavy chain CDRs and a light chain variable region comprising the three light chain CDRs from the antibody produced by the host cell line having ATCC deposit number PTA-8576.
19. The isolated antibody or the antigen-binding fragment of claim 18 , wherein the isolated antibody is a humanized antibody.
20. The isolated antibody or the antigen-binding fragment of claim 18 , wherein the isolated antibody is a chimeric antibody comprising the heavy and light variable regions from the antibody produced by the host cell line having ATCC deposit number PTA-8576.
21. The isolated antibody or the antigen-binding fragment of claim 20 , wherein the chimeric antibody comprises a heavy chain constant region from the heavy chain constant region from a human antibody, and a light chain constant region from the light chain constant region of a human antibody.
22. The isolated antibody or the antigen-binding fragment of claim 18 , wherein the antigen-binding fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′) 2 and a Fv.