Biomarker for selecting patients and related methods

Abstract

The present invention concerns methods for inducing an immune response to an antigen in a patient for treating human disease by administering an immunogenic composition wherein said patient is selected in a patient population of interest. The present invention further concerns methods for determining whether a subject is or is not susceptible to developing a prophylactic or therapeutic immune response after such treatment.

1 - 11 . (canceled) 
     
     
         12 . An ex-vivo method for testing whether a patient will respond therapeutically to a method of treatment comprising administration of an immunogenic composition or for predicting whether a patient is or is not susceptible to survive longer after administration of an immunogenic composition, wherein the method comprises:
 obtaining a blood sample from the patient, and   measuring levels of activated NK cells in said blood sample;   wherein low levels of activated NK cells indicate that the patient will develop a prophylactic or therapeutic immune response towards the immunogenic composition or that the patient will have a longer survival rate; and   wherein low levels of activated NK cells are defined as being less than about 5% of the levels of peripheral blood lymphocytes expressing CD16, CD56 and CD96 cell surface antigens.   
     
     
         13 . The method of  claim 12  wherein said method of treatment is a method of treating cancer. 
     
     
         14 . The method of  claim 12  or  13 , wherein said activated NK cells do not express CD3 surface antigen. 
     
     
         15 . The method of  claim 12 , wherein said levels of activated NK cells are measured by flow cytometry. 
     
     
         16 . The method of  claim 12 , wherein said levels of activated NK cells are measured using antibodies specific for CD16, CD56 and CD69 cell surface antigens. 
     
     
         17 . The method of  claim 12 , wherein said blood sample is whole peripheral blood or isolated peripheral blood mononuclear cells. 
     
     
         18 . The method of  claim 12 , wherein said immunogenic composition comprises at least one recombinant vector expressing in vivo all or part of at least one heterologous nucleotide sequence. 
     
     
         19 . The method of  claim 18 , wherein said recombinant vector is a viral vector. 
     
     
         20 . The method of  claim 19 , wherein said viral vector is replication-competent. 
     
     
         21 . The method of  claim 19 , wherein said viral vector is replication-defective. 
     
     
         22 . The method of  claim 19 , wherein said viral vector is a recombinant adenoviral vector. 
     
     
         23 . The method of  claim 19 , wherein said viral vector is a recombinant vaccinia vector. 
     
     
         24 . The method of  claim 23 , wherein said recombinant vaccinia vector is a recombinant MVA vector. 
     
     
         25 . The method of  claim 12 , wherein said immunogenic composition comprises all or part of at least one targeted antigen. 
     
     
         26 . The method of  claim 12 , wherein said patient is treated with a chemotherapeutic agent. 
     
     
         27 . A kit for testing whether a patient will respond therapeutically to a method of treatment comprising administration of an immunogenic composition, wherein the kit comprises:
 antibodies for determining the levels of activated NK cells in a blood sample from the patient, and   instructions for determining whether or not the levels of activated NK cells are low; wherein low levels of activated NK cells are levels of less than 5% of peripheral blood lymphocytes which express CD16, CD56 and CD96 cell surface antigens.   
     
     
         28 . The kit of  claim 27  wherein said antibodies are specific for CD16, CD56 and/or CD69 cell surface antigens.