Methods of treating cancer using anti-LRP1 polyclonal antibodies
Provided herein are agents that hind to binding domain I of LRP1 and mimic the activity of prosaposin in stimulating Tsp-1. Further provided herein are agents that inhibit the function (e.g., the ability to repress Tsp-1) of Protease, Serine 2 (PRSS2) by inhibiting the binding of PRSS2 to LRP1. Methods of using these agents in treating cancer are also provided.
1. A method of treating cancer, the method comprising administering to a subject in need thereof an effective amount of a polyclonal antibody that binds to amino acids 1-172 Low Density Lipoprotein Receptor-related Protein 1 (LRP1).
2. The method of claim 1 , wherein the polyclonal antibody binds to amino acids 151-172 (SEQ ID NO: 3) of LRP1.
3. The method of claim 1 , wherein the polyclonal antibody binds to amino acids 140-164 (SEQ ID NO: 18) of LRP1.
4. The method of claim 1 , wherein the polyclonal antibody binds to amino acids 151-164 (SEQ ID NO: 19) of LRP1.
5. The method of claim 1 , wherein the polyclonal antibody is administered orally, parenterally, intramuscularly, intranasally, intratracheally, intracerebroventricularly, intravenously, or intraperitoneally.
6. The method of claim 1 , wherein the cancer is metastatic.
7. The method of claim 1 , wherein the cancer is biliary tract cancer; bladder cancer; brain cancer; glioblastoma; medulloblastoma; breast cancer; cervical cancer; choriocarcinoma; colon cancer; endometrial cancer; esophageal cancer; gastric cancer; hematological neoplasm; acute lymphocytic leukemia; myelogenous leukemia; multiple myeloma; AIDS-associated leukemia; adult T-cell leukemia; lymphoma; intraepithelial neoplasm; Bowen's disease; Paget's disease; liver cancer; lung cancer; lymphomas; Hodgkin's disease; lymphocytic lymphoma; neuroblastoma; oral cancer; squamous cell carcinoma; ovarian cancer; pancreatic cancer; prostate cancer; rectal cancer; sarcoma; leiomyosarcoma; rhabdomyosarcoma; liposarcoma; fibrosarcoma; osteosarcoma; skin cancer; testicular cancer; stromal tumor; germ cell tumor; thyroid cancer; or renal cancer.
8. The method of claim 7 , wherein the cancer is prostate cancer, breast cancer, ovarian cancer, or pancreatic cancer.
9. The method of claim 1 , wherein the polyclonal antibody inhibits the ability of Protease, serine 2 (PRSS2) to repress Tsp-1.
10. The method of claim 1 , wherein the polyclonal antibody inhibits binding of PRSS2 to Low Density Lipoprotein Receptor-related Protein 1 (LRP1).