Methods of Therapy and Diagnosis Using Immunotargeting of CD84Hy1-expressing Cells

Abstract

Certain cells, including types of cancer cells such as lymphomas, are capable of expressing high levels of CD84Hy1. Immunotargeting using CD84Hy1 polypeptides, nucleic acids encoding for CD84Hy1 polypeptides and anti-CD84Hy1 antibodies provides a method of killing or inhibiting that growth of CD84HY1 Protein-expressing cancer cells. Methods of immunotherapy and diagnosis of disorders associated with CD84Hy1 protein-expressing cells are described.

1 . A pharmaceutical composition comprising an anti-CD84Hy1 antibody or antibody fragment thereof that binds CD84Hy1-expressing lymphoid or myeloid cells in a hematopoietic-based cancer. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the antibody is a monoclonal antibody or antibody fragment thereof. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the antibody is a human or humanized antibody. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the antibody is administered in an amount effective to kill or inhibit the growth of said lymphoid or myeloid cells. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the antibody is conjugated to a second molecule. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the second molecule is a radioisotope, toxin or drug. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the hematopoietic-based cancer is selected from the group consisting of acute myelogenous leukemia, acute myelomonocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B cell large cell lymphoma, malignant lymphoma, lymphosarcoma cell leukemia, B-cell lymphoma, T-cell lymphoma, acute myeloid leukemia, and Hodgkin's Disease. 
     
     
         8 . A method of treating a hematopoietic-based cancer comprising administering to a subject in need of treatment the pharmaceutical composition of  claim 1 . 
     
     
         9 . A method of targeting a CD84Hy1 polypeptide on the surface of lymphoid or myeloid cells in a hematopoietic-based cancer comprising administering the pharmaceutical composition of  claim 1 . 
     
     
         10 . A method of killing or inhibiting the growth of CD84Hy1-expressing lymphoid or myeloid cells in a hematopoietic-based cancer comprising administering the pharmaceutical composition of  claim 1 . 
     
     
         11 . A method of treating a hematopoietic-based cancer, comprising administering to a subject in need of treatment a CD84Hy1 targeting compound selected from the group consisting of a CD84Hy1 vaccine, a nucleic acid encoding a CD84Hy1 polypeptide, and a CD84Hy1 antigen-presenting cell. 
     
     
         12 . A method of killing or inhibiting the growth of CD84Hy1-expressing lymphoid or myeloid cells in a hematopoietic-based cancer comprising administering to said cells a CD84Hy1 targeting compound selected from the group consisting of a CD84Hy1 vaccine, a nucleic acid encoding a CD84Hy1 polypeptide, and a CD84Hy1 antigen-presenting cell. 
     
     
         13 . The method of  claim 11  or  12 , wherein the CD84Hy1 vaccine comprises a nucleic acid that encodes a CD84Hy1 polypeptide or immunogenic fragment thereof within a recombinant vector. 
     
     
         14 . The method of  claim 11  or  12 , wherein the nucleic acid comprises a nucleic acid that encodes a CD84Hy1 polypeptide or immunogenic fragment thereof within a recombinant vector. 
     
     
         15 . The method of  claims 11  or  12  wherein the CD84Hy1 antigen-presenting cell comprises a nucleic acid that encodes a CD84Hy1 polypeptide or immunogenic fragment thereof within a recombinant vector. 
     
     
         16 . The method of any one of  claims 8  through  15 , wherein the hematopoietic-based cancer is selected from the group consisting of acute myelogenous leukemia, acute myelomonocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B cell large cell lymphoma, malignant lymphoma, lymphosarcoma cell leukemia, B-cell lymphoma, T-cell lymphoma, acute myeloid leukemia, and Hodgkin's Disease. 
     
     
         17 . The method of any one of  claims 8  through  15 , wherein the cells are contacted with a second therapeutic agent. 
     
     
         18 . The method of any one of  claims 8  through  10 , wherein the antibody is administered to a subject in a dosage range of about 0.1 to about 10 mg/kg body weight. 
     
     
         19 . The method of any one of  claims 8  through  10 , wherein said antibody is administered in a sterile preparation together with a pharmaceutically acceptable carrier therefor. 
     
     
         20 . The method of  claim 11 , wherein said CD84Hy1 targeting compound is administered in a sterile preparation together with a pharmaceutically acceptable carrier therefor. 
     
     
         21 . A method of diagnosing a hematopoietic-based cancer comprising the steps of:
 a) detecting or measuring the expression of a CD84Hy1 protein on a cell; and   b) comparing said expression to a standard indicative of said disease.   
     
     
         22 . A method of diagnosing a hematopoietic-based cancer comprising the steps of:
 a) detecting or measuring the expression of a CD84Hy1 protein on a cell; and   b) comparing said expression to normal tissue.   
     
     
         23 . The method of  claim 21  or  22 , wherein the hematopoietic-based cancer is selected from the group consisting of acute myelogenous leukemia, acute myelomonocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B cell large cell lymphoma, malignant lymphoma, lymphosarcoma cell leukemia, B-cell lymphoma, T-cell lymphoma, acute myeloid leukemia, and Hodgkin's Disease. 
     
     
         24 . The method of  claim 21  or  22 , wherein the expression is CD84Hy1 mRNA expression. 
     
     
         25 . An antibody that binds with high affinity to a CD84Hy1 polypeptide or immunogenic fragment thereof. 
     
     
         26 . The antibody of  claim 25 , wherein the antibody is a monoclonal antibody or antibody fragment thereof. 
     
     
         27 . The antibody of  claim 25 , wherein the antibody is human or humanized. 
     
     
         28 . The antibody of  claim 25 , wherein the antibody is conjugated to a second molecule. 
     
     
         29 . The antibody of  claim 28 , wherein the second molecule is a radioisotope, toxin or drug. 
     
     
         30 . A method of treating an autoimmune disorder comprising administering to a subject in need of treatment, a CD84Hy1 targeting compound selected from the group consisting of a CD84Hy1 antibody or antibody fragment thereof, a CD84Hy1 vaccine, a nucleic acid encoding a CD84Hy1 polypeptide, and a CD84Hy1 antigen-presenting cell. 
     
     
         31 . The method of  claim 30 , wherein the vaccine comprises a CD84Hy1 polypeptide or immunogenic fragment thereof. 
     
     
         32 . The method of  claim 30 , wherein the nucleic acid comprises a nucleic acid that encodes a CD84Hy1 polypeptide or immunogenic fragment thereof within a recombinant vector. 
     
     
         33 . The method of  claim 30 , wherein the antigen-presenting cell comprises a nucleic acid encoding CD84Hy1 or immunogenic fragment thereof within a recombinant vector. 
     
     
         34 . A method of treating or preventing rejection of transplanted tissues or organs comprising administering a to a subject in need of treatment, a CD84Hy1 targeting compound selected from the group consisting of a CD84Hy1 antibody or antibody fragment thereof, a CD84Hy1 vaccine, a nucleic acid encoding a CD84Hy1 polypeptide, and a CD84Hy1 antigen-presenting cell. 
     
     
         35 . The method of  claim 34 , wherein the vaccine comprises a CD84Hy1 polypeptide or immunogenic fragment thereof. 
     
     
         36 . The method of  claim 34 , wherein the nucleic acid comprises a nucleic acid that encodes a CD84Hy1 polypeptide or immunogenic fragment thereof within a recombinant vector. 
     
     
         37 . The method of  claim 34 , wherein the antigen-presenting cell comprises a nucleic acid encoding CD84Hy1 or immunogenic fragment thereof within a recombinant vector.