Antibody and antigen recognizing tumor-initiating cells and use thereof

Abstract

Disclosed is a method for searching, identifying, or validating a marker CACNA2D1 of tumor-initiating cells. The method comprises a step of immunizing an animal using HEP-12 cells originating from a recurrent tumor and rich in originating cells. Also disclosed is a monoclonal antibody specially recognizing CACNA2D1 or antigen-binding fragments thereof, and the use thereof for treating or preventing tumors or diseases or conditions related to CACNA2D1.

1 .- 18 . (canceled) 
     
     
         19 . A method for seeking, differentiating or identifying a marker of tumor initiating cells or a target for tumor treatment, wherein this method comprises immunizing an animal using cells from recurrent tumor sources rich in tumor initiating cells, isolating at least one antibody that specifically binds to the cells from recurrent tumor sources rich in tumor initiating cells, and using the isolated antibody to identify the marker of tumor initiating cells or the target for tumor treatment. 
     
     
         20 .- 24 . (canceled) 
     
     
         25 . A method for treating a tumor in a subject, comprising:
 adopting the method of  claim 19  to seek, differentiate or identify a marker of tumor initiating cells or a target for tumor treatment;   screening and developing an anti-tumor agent based on the marker or the target, wherein the anti-tumor agent reduces gene expression and/or protein activity of the marker or the target, or causes cytotoxic reaction after targeting the marker or the target;   administering a therapeutically effective amount of the anti-tumor agent to the subject.   
     
     
         26 . The method of  claim 25 , wherein the anti-tumor agent is an antibody or an antigen binding fragment, a single-stranded or double-stranded oligonucleotide, a nucleic acid molecule, a short peptide, or a small molecular compound agent thereof. 
     
     
         27 .- 28 . (canceled) 
     
     
         29 . A kit comprising a first nucleic acid molecule, wherein the first nucleic acid molecule specifically binds to a second nucleic acid molecule that encodes CACNA2D1. 
     
     
         30 . A method for diagnosing a tumor in a subject, wherein the tumor has CACNA2D1 on its surface and the method comprises administrating an agent that detects the presence of CACNA2D1. 
     
     
         31 . A method for treating a tumor in a subject, wherein the tumor has CACNA2D1 on its surface and the method comprises administrating an agent that binds to CACNA2D1 on the tumor and inhibits growth of the tumor in the subject. 
     
     
         32 . The method of  claim 31 , wherein the agent is an antibody. 
     
     
         33 . The method of  claim 32 , wherein the antibody is a monoclonal antibody. 
     
     
         34 . The method of  claim 31 , wherein the agent comprises at least one CDR of the monoclonal antibody 1B50-1. 
     
     
         35 . The method of  claim 32 , wherein the agent comprises an antigen binding region of an antibody that binds to CACNA2D1 on the tumor cells. 
     
     
         36 . A method for treating a tumor in a subject, wherein the tumor has CACNA2D1 on its surface and the method comprises administrating to the subject an agent that interferes with expression of CACNA2D1 on the tumor. 
     
     
         37 . The method of  claim 36 , wherein the agent interferes with the RNA production of CACNA2D1 or interferes with the activity of the RNA of CACNA2D1. 
     
     
         38 . The method of  claim 31 , wherein the method further comprises administrating another anti-tumor agent to the subject. 
     
     
         39 . The method of  claim 38 , wherein the other anti-tumor agent is a chemotherapeutic agent or a biotherapeutic agent. 
     
     
         40 . The method of  claim 31 , wherein the method further comprises treating the subject with a radiotherapy and/or a surgery. 
     
     
         41 . The method of  claim 31 , wherein the tumor is a solid tumor. 
     
     
         42 . The method of  claim 41 , wherein the tumor is liver cancer, colon cancer, rectal cancer, kidney cancer, esophagus cancer, gastric cancer, lung cancer, breast cancer, prostatic cancer or another tumor involving the presence of CACNA2D1 on its surface. 
     
     
         43 . The method of  claim 41 , wherein the tumor is hepatocellular carcinoma. 
     
     
         44 . A method for treating a tumor in a subject, wherein the tumor has CACNA2D1 on its surface and the method comprises administering to the subject
 (i) an agent that binds to CACNA2D1 on the tumor; or   (ii) an agent that interferes with the RNA production of CACNA2D1 on the tumor.