Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof

Abstract

Small animal models for assessing immunomodulatory effects of compounds are provided.

1 . A method of assessing the immunomodulatory effect of a molecule expressed by cancer cells comprising: 
 administering a molecule naturally expressed by cancer cells, cancer cells and lymphocytes to a subject; and    monitoring the rate of growth of the cancer cells,    wherein the molecule is deemed to have an immunomodulatory effect when any change in the growth rate of the cancer cells is observed compared to the rate of growth when the cancer cells and donor lymphocytes are administered alone.    
     
     
         2 . A method as in  claim 1  wherein the molecule is considered immune enhancing where a reduction in the rate of growth of the cancer cells is observed compared to the rate of growth when the cancer cells and donor lymphocytes are administered alone.  
     
     
         3 . A method as in  claim 1  wherein the molecule is considered immunosuppressive where a greater rate of growth of the cancer cells is observed compared to the rate of growth when the cancer cells and donor lymphocytes are administered alone.  
     
     
         4 . A method as in  claim 1  wherein the molecule naturally expressed by a cancer cell is administered by injecting cells that naturally express the compound.  
     
     
         5 . A method as in  claim 1  wherein the molecule naturally expressed by a cancer cell is administered by injecting cells that have been engineered to express the molecule.  
     
     
         6 . A method as in  claim 1  further comprising identifying the molecule expressed by cancer cells from a database.  
     
     
         7 . A method as in  claim 1  further comprising identifying the molecule expressed by cancer cells experimentally.  
     
     
         8 . The method of  claim 1 , wherein the lymphocytes are human.  
     
     
         9 . The method of  claim 8  wherein the human lymphocytes are selected from the group consisting of peripheral blood lymphocytes (PBLs), T cells, B cells, and dendritic cells.  
     
     
         10 . The method of  claim 1 , wherein the lymphocytes are human peripheral blood lymphocytes (PBLs).  
     
     
         11 . The method of  claim 1  wherein the number of lymphocytes administered is insufficient to reduce the rate of growth of cancer cells.  
     
     
         12 . The method of  claim 1  wherein the number of lymphocytes administered is less than the number of cancer cells administered.  
     
     
         13 . The method of  claim 1  wherein the number of lymphocytes administered is from about 1 million cells to about 2 million cells.  
     
     
         14 . The method of  claim 1  wherein the number of lymphocytes administered is sufficient to reduce the rate of growth of cancer cells.  
     
     
         15 . The method of  claim 1  wherein the number of lymphocytes administered is greater than or equal to the number of cancer cells administered.  
     
     
         16 . The method of  claim 1  wherein the number of lymphocytes administered is from about 5 million cells to about 10 million cells.  
     
     
         17 . The method of  claim 1 , wherein administering of cancer cells comprises injecting at least one lymphoma cell line selected from the group consisting of RAJI and Namalwa into the subject.  
     
     
         18 . The method of  claim 1  wherein the subject is an immunodeficient mouse.  
     
     
         19 . The method of  claim 1  wherein the number of lymphocytes administered is sufficient to slow the growth of the cancer cells and the molecule expressed by cancer cells is considered immunosuppressive where the rate of growth of the cancer cells observed is higher compared to the rate of growth when the cancer cells and lymphocytes are administered alone.  
     
     
         20 . The method of  claim 1  wherein the number of lymphocytes administered is insufficient to slow the growth of the cancer cells and the molecule expressed by cancer cells is considered immune-enhancing where the rate of growth of the cancer cells observed is lowered compared to the rate of growth when the cancer cells and lymphocytes are administered alone.  
     
     
         21 . A method as in  claim 1  further comprising determining the rate of growth of the cancer cells by administering lymphocytes and cancer cells alone to a control subject.  
     
     
         22 . A method as in  claim 1  further comprising determining the rate of growth of the cancer cells by administering lymphocytes and cancer cells alone to the subject prior to administering the molecule that is expressed by cancer cells.  
     
     
         23 . A method of assessing the immunomodulatory effect of a compound comprising the steps of: 
 administering a compound to be assessed, cancer cells and lymphocytes to a subject; and    monitoring the rate of growth of the cancer cells,    wherein the compound is deemed to have an immunomodulatory effect where any change in the growth rate of the cancer cells is observed compared to the rate of growth when the cancer cells and donor lymphocytes are administered alone.    
     
     
         24 . The method of  claim 23  wherein the compound is considered immune enhancing where a reduction in the rate of growth of the cancer cells is observed compared to the rate of growth when the cancer cells and donor lymphocytes are administered alone.  
     
     
         25 . The method of  claim 23  wherein the compound is considered immunosuppressive when the rate of growth of the cancer cells in the presence of the compound is greater than the rate of growth when the cancer cells and donor lymphocytes are administered alone.  
     
     
         26 . The method of  claim 23  wherein the compound to be assessed is an antibody.  
     
     
         27 . The method of  claim 23  wherein administering of cancer cells comprises injecting at least one lymphoma cell line selected from the group consisting of RAJI and Namalwa into the subject.  
     
     
         28 . The method of  claim 23  wherein the cancer cells administered express an immunosuppressive molecule.  
     
     
         29 . The method of  claim 23  wherein the cancer cells administered express CD200.  
     
     
         30 . The method of  claim 23  wherein the expression of CD 200 is upregulated by the cancer cells administered.  
     
     
         31 . The method of  claim 23  wherein the lymphocytes are human.  
     
     
         32 . The method of  claim 31  wherein the human lymphocytes are selected from the group consisting of peripheral blood lymphocytes (PBLs), T cells, B cells, and dendritic cells.  
     
     
         33 . The method of  claim 23  wherein the lymphocytes are human peripheral blood lymphocytes (PBLs).  
     
     
         34 . The method of  claim 33  wherein the number of human PBLs administered is less than the number of cancer cells administered.  
     
     
         35 . The method of  claim 33  wherein the number of human PBLs administered is from about I million cells to about 2 million cells.  
     
     
         36 . The method of  claim 33  wherein the number of human PBLs administered is greater than or equal to the number of cancer cells administered.  
     
     
         37 . The method of  claim 33  wherein the number of human PBLs administered is from about 5 million cells to about 10 million cells.  
     
     
         38 . The method of  claim 23  wherein the subject is an immunodeficient mouse.  
     
     
         39 . The method of  claim 23  wherein the number of lymphocytes administered is sufficient to slow the rate of growth of the cancer cells when administered with the cancer cells alone, the compound is considered immunosuppressive when the rate of growth of the cancer cells in the presence of the compound is greater than the rate of growth when the cancer cells and donor lymphocytes are administered alone.  
     
     
         40 . The method of  claim 23  wherein the number of lymphocytes administered is not sufficient to slow the rate of growth of cancer cells when administered with the cancer cells alone, and the compound is considered immune enhancing where a reduction in the rate of growth of the cancer cells is observed compared to the rate of growth when the cancer cells and donor lymphocytes are administered alone.  
     
     
         41 . A method of assessing the immunomodulatory effect of a compound comprising the steps of: 
 administering a compound to be assessed, cancer cells and lymphocytes to a subject, the amount of lymphocytes being insufficient to reduce the growth rate of the cancer cells; and    monitoring the rate of growth of the cancer cells,    wherein the compound is considered immune enhancing where a reduction in the rate of growth of the cancer cells is observed compared to the rate of growth when the cancer cells and donor lymphocytes are administered alone.    
     
     
         42 . The method of  claim 41  wherein the cancer cells administered express an immunosuppressive molecule.  
     
     
         43 . The method of  claim 41  wherein the cancer cells administered express CD200.  
     
     
         44 . The method of  claim 41  wherein the expression of CD200 is upregulated by the cancer cells administered.  
     
     
         45 . A method of assessing the immunomodulatory effect of a compound comprising the steps of: 
 administering a compound to be assessed, cancer cells and more lymphocytes to a subject, the amount of lymphocytes being sufficient to reduce the growth rate of the cancer cells; and    monitoring the rate of growth of the cancer cells,    wherein the compound is considered immunosuppressive when the rate of growth of the cancer cells in the presence of the compound is greater than the rate of growth when the cancer cells and donor lymphocytes are administered alone.    
     
     
         46 . The method of  claim 45  wherein the cancer cells administered express an immunosuppressive molecule.  
     
     
         47 . The method of  claim 45  wherein the cancer cells administered express CD200.  
     
     
         48 . The method of  claim 45  wherein the expression of CD200 is upregulated by the cancer cells administered.