Predicting cancer progression

Abstract

A method of predicting the likelihood of cancer relapse in a patient undergoing treatment for cancer is provided. The binding response level of an immunoreactive material (IM) comprising thymidine kinase 1 (TK1) protein is determined in a body fluid sample of a patient and the likelihood of relapse of the cancer disease is predicted based on this determined IM binding response level. Those patients that run a risk of cancer progress and relapse 1-15 years after the cancer treatment may be identified directly by the IM binding response level within a few months following initiation of the treatment.

1 . A method of predicting cancer relapse in a subject undergoing treatment for cancer, the method comprising:
 (i) contacting an antibody that binds specifically to a thymidine kinase 1 (TK1) protein with a blood serum sample from the subject;   (ii) determining the amount of antibody binding to the TK1 protein and/or to a TK1 protein complex in the blood serum sample, to obtain a reference amount of antibody binding;   (iii) contacting the antibody that binds specifically to the thymidine kinase 1 (TK1) protein with a blood serum sample from the subject after undergoing the treatment for cancer;   (iv) determining the amount of antibody binding to the TK1 protein and/or the TK1 protein complex in the blood serum sample after undergoing the treatment for cancer to obtain a post-treatment amount of antibody binding;   (v) comparing the post-treatment amount of antibody binding to the reference amount of antibody binding; and   (vi) predicting an increased likelihood of cancer relapse if the ratio of the post-treatment amount of antibody binding to the reference amount of antibody binding is greater than one.   
     
     
         2 . The method according to  claim 1 , wherein the reference amount of antibody binding is determined with a blood serum sample from the subject before initiating the treatment for cancer. 
     
     
         3 . The method according to  claim 1 , wherein the post-treatment amount of antibody binding is determined with a blood serum sample from the subject within one to six months following the treatment for cancer. 
     
     
         4 . The method according to  claim 3 , wherein the post-treatment amount of antibody binding is determined with a blood serum sample from the subject about three months following the treatment for cancer. 
     
     
         5 . The method according to  claim 1 , wherein the antibody binds specifically to a C-terminal portion of the TK1 protein. 
     
     
         6 . The method according to  claim 1 , wherein the antibody is produced against a peptide sequence selected from:
 amino acid sequence according to SEQ ID NO: 1; and   amino acid sequence according to SEQ ID NO: 2.   
     
     
         7 . The method according to  claim 1 , wherein determining the amount of antibody binding comprises measuring the amount of antibody binding by an enhanced chemoluminescence (ECL) dot blot immunoassay. 
     
     
         8 . The method according to  claim 1 , wherein the cancer is a solid tumor cancer. 
     
     
         9 . The method according to  claim 1 , wherein predicting the increased likelihood of cancer relapse is based directly on the post-treatment amount of antibody binding and the reference amount of antibody binding. 
     
     
         10 . The method according to  claim 1 , wherein the increased likelihood of cancer relapse is predicted without determining an enzyme activity level of TK1. 
     
     
         11 . The method according to  claim 1 , wherein the TK1 protein complex comprises the TK1 protein and a protein or polypeptide. 
     
     
         12 . A method of predicting cancer relapse in a subject undergoing treatment for cancer, the method comprising:
 (i) contacting an antibody that binds specifically to a thymidine kinase 1 (TK1) protein with a blood serum sample from the subject;   (ii) determining the amount of antibody binding to the TK1 protein and/or a TK1 protein complex in the blood serum sample;   (iii) comparing the determined amount of antibody binding from step (ii) with a reference amount of antibody binding obtained from blood serum samples of healthy tumor-free subjects; and   (iv) predicting an increased likelihood of cancer relapse if the determined amount of antibody binding is higher than the reference amount of antibody binding.   
     
     
         13 . The method according to  claim 13 , wherein the increased likelihood of cancer relapse is predicted if the determined amount of antibody binding is at least twice the reference amount of antibody binding. 
     
     
         14 . A method of predicting cancer relapse in a subject undergoing treatment for cancer, the method comprising:
 (i) contacting an antibody that binds specifically to a thymidine kinase 1 (TK1) protein with a blood serum sample from the subject;   (ii) determining the amount of antibody binding to the TK1 protein and/or a TK1 protein comprising complex in the blood serum sample;   (iii) generating a relation between an amount of antibody binding specifically to a recombinant TK1 protein and a concentration level of the TK1 protein and/or TK1 protein comprising complex;   (iv) determining the concentration level of the TK1 protein and/or a TK1 protein comprising complex in the blood serum sample from the amount of antibody binding in step (ii) and the generated relation in step (iii); and   (v) predicting an increased likelihood of cancer relapse if the determined concentration level of the TK1 protein and/or TK1 protein complex in the blood serum sample exceeds 2 pM.   
     
     
         15 . The method according to  claim 11 , wherein the protein or polypeptide is an inhibitor or an activator of the TK1 protein.