Bispecific aptamer for treating cancer

Abstract

Bispecific aptamers having a first end that specifically binds to a first tumor specific marker, tumor antigen, or viral protein and a second end that specifically binds to a second tumor specific marker, tumor antigen, or viral protein are provide. The bispecific aptamers can be used to treat cancer or virally infected cells. Generally, the bispecific aptamers bind to two surface proteins, preferably different proteins, on the same cell. In a preferred embodiment the bispecific aptamers bind to two different tumor markers, tumor antigens, tumor specific proteins and combinations thereof.

I claim: 
     
         1 . A bispecific aptamer comprising a first end that specifically binds to a first tumor specific marker, tumor antigen, or viral protein and a second end that specifically binds to a second tumor specific marker, tumor antigen, or viral protein. 
     
     
         2 . The bispecific aptamer of  claim 1 , wherein the aptamer comprises ssRNA or ssDNA. 
     
     
         3 . The bispecific aptamer of  claim 1 , wherein the first tumor specific marker is EpCAM and the second tumor specific marker is CD44. 
     
     
         4 . The bispecific aptamer of  claim 1  wherein the first and second tumor specific markers are selected from the group consisting of Alpha-fetoprotein (AFP), Beta-2-microglobulin (B2M), Beta-human chorionic gonadotropin (Beta-hCG), C-kit/CDI 17, CA15-3/CA27.29, CA125, CA19-9, Calcitonin, Carcinoembryonic antigen (CEA), CD20, Chromogranin A (CgA), Cytokeratin fragment 21-1, HE4, Neuron-specific enolase (NSE), Programmed death ligand I (PD-LI), Prostate-specific antigen (PSA), Thyroglobulin, Epithelial tumor antigen (ETA), Melanoma-associated antigen (MAGE), and MUC-1. 
     
     
         5 . A pharmaceutical composition comprising the bispecific aptamer of  claim 1 . 
     
     
         6 . The pharmaceutical composition of  claim 5 , further comprising a pharmaceutically acceptable excipient. 
     
     
         7 . A method for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of the bispecific aptamer of  claim 1  or the pharmaceutical composition of  claim 5  to inhibit or reduce tumor growth. 
     
     
         8 . A method for reducing tumor burden in a subject in need thereof, comprising administering to the subject an effective amount of the bispecific aptamer of  claim 1 - 4  or the pharmaceutical composition of  claim 5  to inhibit or reduce tumor growth. 
     
     
         9 . The method of  claim 7 , wherein the subject has ovarian cancer. 
     
     
         10 . The method of  claim 7 , wherein the subject has bone sarcoma, osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant giant cell tumor, fibrosarcoma of bone, chordoma, periosteal sarcoma, soft-tissue sarcomas, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, neurilemmoma, rhabdomyosarcoma, synovial sarcoma; brain tumors, glioma, astrocytoma, brain stem glioma, ependymoma, oligodendroglioma, nonglial tumor, acoustic neurinoma, craniopharyngioma, medulloblastoma, meningioma, pineocytoma, pineoblastoma, primary brain lymphoma; breast cancer, adenocarcinoma, lobular (small cell) carcinoma, intraductal carcinoma, medullary breast cancer, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget's disease, and inflammatory breast cancer;
 adrenal cancer, pheochromocytom and adrenocortical carcinoma; thyroid cancer, papillary or follicular thyroid cancer, medullary thyroid cancer and anaplastic thyroid cancer; pancreatic cancer, insulinoma, gastrinoma, glucagonoma, vipoma, somatostatin-secreting tumor, and carcinoid or islet cell tumor; pituitary cancers, Cushing's disease, prolactin-secreting tumor, acromegaly, and diabetes insipius; eye cancers, ocular melanoma, iris melanoma, choroidal melanoma, and ciliary body melanoma, and retinoblastoma; vaginal cancers—squamous cell carcinoma, adenocarcinoma, and melanoma; vulvar cancer—squamous cell carcinoma, melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, and Paget's disease; cervical cancers: squamous cell carcinoma, and adenocarcinoma; uterine cancers: endometrial carcinoma and uterine sarcoma; ovarian cancers: ovarian epithelial carcinoma, borderline tumor, germ cell tumor, and stromal tumor; esophageal cancers including, but not limited to, squamous cancer, adenocarcinoma, adenoid cyctic carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, sarcoma, melanoma, plasmacytoma, verrucous carcinoma, and oat cell (small cell) carcinoma; stomach cancers: adenocarcinoma, fungating (polypoid), ulcerating, superficial spreading, diffusely spreading, malignant lymphoma, liposarcoma, fibrosarcoma, and carcinosarcoma; colon cancers; rectal cancers; liver cancers: hepatocellular carcinoma and hepatoblastoma, gallbladder cancers: adenocarcinoma; cholangiocarcinomas: papillary, nodular, and diffuse; lung cancers: non-small cell lung cancer, squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large-cell carcinoma and small-cell lung cancer; testicular cancers: germinal tumor, seminoma, anaplastic, classic (typical), spermatocytic, nonseminoma, embryonal carcinoma, teratoma carcinoma, choriocarcinoma (yolk-sac tumor), prostate cancers: adenocarcinoma, leiomyosarcoma, and rhabdomyosarcoma; penal cancers; oral cancers: squamous cell carcinoma; basal cancers;   salivary gland cancers: adenocarcinoma, mucoepidermoid carcinoma, and adenoidcystic carcinoma; pharynx cancers: squamous cell cancer, and verrucous; skin cancers: basal cell carcinoma, squamous cell carcinoma and melanoma, superficial spreading melanoma, nodular melanoma, lentigo malignant melanoma, acral lentiginous melanoma; kidney cancers including, but not limited to, renal cell cancer, adenocarcinoma, hypernephroma, fibrosarcoma, transitional cell cancer (renal pelvis and/or ureter); Wilms' tumor; bladder cancers: transitional cell carcinoma, squamous cell cancer, adenocarcinoma, carcinosarcoma;   myxosarcoma, osteogenic sarcoma, endotheliosarcoma, lymphangioendotheliosarcoma, mesothelioma, synovioma, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, and gastric cancer.