Method for upregulating antigen expression

Abstract

The present invention relates to radioimmunoconjugates that are capable of upregulating expression of one or more antigens. The upregulated antigens can be the antigens that are targeted by the radioimmunoconjugates or different antigens expressed on the same cells. The present invention also relates to methods of treating cancer and diseases and disorders of the immune system by utilizing this enhanced expression of antigens.

1 . A method of using a radioimmunoconjugate to upregulate expression of CD20 on the surface of B-cell cancer cells in a subject comprising:
 administering to said subject having B cell cancer cells, a radioimmunoconjugate comprising:
 a monoclonal antibody specific for CD37, 
 an optional linker, and 
 a radionuclide, wherein 
 after administration of radioimmunoconjugate to said subject, said subject is administered an anti-CD20 antibody therapy in a single administration or in a repeated administration pattern. 
   
     
     
         2 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein said subject has a B-cell malignancy selected from the group consisting of non-Hodgkin lymphoma, acute Lymphoblastic Leukemia, and chronic lymphocytic leukemia. 
     
     
         22 . The method of  claim 1 , wherein the administration of anti-CD20 antibody therapy is at least one day after radioimmunoconjugate administration. 
     
     
         23 . The method of  claim 1 , wherein the antiCD20 antibody therapy comprises rituximab or obinutuzumab. 
     
     
         24 . The method of  claim 1 , wherein the upregulation of expression of CD20 on the surface of B-cell cancer cells in said subject is done prior to immunotherapy or immunoconjugate therapy. 
     
     
         25 . The method of  claim 24 , wherein the subject has a B-cell malignancy selected from the group consisting of non-Hodgkin lymphoma and chronic lymphocytic leukemia. 
     
     
         26 . The method of  claim 1 , wherein the monoclonal antibody specific for CD37 is HH1. 
     
     
         27 . The method of  claim 1 , wherein the linker is a chelating linker selected from the group consisting of p-SCN-bn-DOTA, DOTA-NHS-ester, p-SCN-Bn-DTPA and CHX-A″-DTPA. 
     
     
         28 . The method of  claim 1 , wherein the radionuclide is selected from the group consistin of  47 SC,  67 Cu,  90 y,  105 Rh,  117 mSn,  131 I,  149 Tb,  153 Sm,  161 Tb,  165 Dy,  186 Re,  188 Re,  211 At,  212 Pb,  212 Bi,  213 Bi  223 Ra,  224 Ra,  225 Ac, and  227 Th. 
     
     
         29 . The method of  claim 1 , wherein the radioimmunoconjugate is formulated as a pharmaceutical composition. 
     
     
         30 . The method of  claim 29 , wherein the pharmaceutical composition comprises one or more pharmaceutically acceptable carriers or adjuvants. 
     
     
         31 . The method of  claim 1 , wherein said anti-CD20 antibody therapy is administered to said subject after administration of said radioimmunoconjugate in 0-15 days. 
     
     
         32 . A method of treatment of a of a B-cell malignancy selected from the group consisting of non-Hodgkin lymphoma, acute Lymphoblastic Leukemia, and chronic lymphocytic leukemia, comprising:
 administration of radioimmunoconjugate comprising,   a monoclonal antibody targeting CD37,   an optional linker,   a radionuclide, and   administration of:
 an anti-CD20 antibody, wherein 
   the radioimmunoconjugate upregulates antigen expression of an antigen expressed on the surface of B-cell cancer cells, the upregulated antigen is CD20, the upregulation is followed by anti-CD20 antibody therapy in a single administration or in a repeated administration pattern, and the administration of anti-CD20 antibody is after administration of radioimmunoconjugate.   
     
     
         33 . The method of  claim 32 , wherein said anti-CD20 antibody therapy is administered to said subject after administration of said radioimmunoconjugate in 0-15 days.