Tumor immunity

Abstract

Disclosed herein are materials and methods for treating cancer. In particular, compositions for stimulating tumor immunity through modulation of MFG-E8 are provided.

1 . A method of treating a cancer or cancer symptom in a subject, the method comprising administering to the subject an effective amount of one or more tumor cell antigens that elicit an immune response against a tumor and an MFG-E8, wherein the MFG-E8 inhibitor is selected from the group consisting of an anti-MFG-E8 antibody, an anti-phosphatidyl serine antibody, an MFG-E8 polypeptide that lacks the ability to bind integrins; and an MFG-E8 polypeptide that lacks the ability to bind phosphatidyl serine. 
     
     
         2 . The method of  claim 1 , wherein the method comprises administering a composition comprising an effective amount of one or more tumor cell antigens that elicit an immune response against a tumor and an MFG-E8 inhibitor. 
     
     
         3 . The method of  claim 1 , wherein the method comprises administering a first composition comprising an effective amount of one or more tumor cell antigens that elicit an immune response against a tumor and administering a second composition comprising an effective amount of an MFG-E8 inhibitor. 
     
     
         4 . The method of  claim 1  wherein the step of administering an effective amount of one or more tumor cell antigens comprises administering autologous tumor cells. 
     
     
         5 . The method of  claim 4 , wherein the autologous tumor cells express GM-CSF. 
     
     
         6 . The method of  claim 5 , wherein the autologous tumor cells harbor recombinant DNA encoding GM-CSF. 
     
     
         7 . The method of  claim 4 , wherein the autologous tumor cells are proliferation incompetent or have been irradiated. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , further comprising administering a GM-CSF expressing cell to the subject. 
     
     
         11 . The method of  claim 10 , wherein the GM-CSF expressing cell secretes GM-CSF. 
     
     
         12 . The method of  claim 10 , wherein the GM-CSF expressing cell is a cell line engineered to express GM-CSF. 
     
     
         13 . The method of  claim 10 , wherein GM-CSF expressing cell harbors recombinant DNA encoding GM-CSF. 
     
     
         14 . The method of  claim 12 , wherein the cell line is K562. 
     
     
         15 . The method of  claim 10 , wherein the GM-CSF expressing cell is proliferation incompetent, or has been irradiated. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , further comprising administering GM-CSF to the subject. 
     
     
         18 . The method of  claim 1 , further comprising administering an anti-CTLA-4 antibody to the subject. 
     
     
         19 . The method of  claim 1  wherein the cancer is selected from the group consisting of melanoma, breast cancer, lung cancer, kidney cancer, ovarian cancer, colon cancer and leukemia. 
     
     
         20 . The method of  claim 1 , wherein the antibody is at least one of a monoclonal antibody, a polyclonal antibody, an Fab fragment, a chimeric antibody, a humanized antibody or a single chain antibody. 
     
     
         21 . The method of  claim 1 , wherein the effective amount of one or more tumor cell antigens that elicit an immune response against a tumor and an MFG-E8 inhibitor is administered by injection, infusion or inhalation. 
     
     
         22 . The method of  claim 1 , further comprising administering a conventional cancer therapeutic to the subject. 
     
     
         23 . The method of  claim 22 , wherein the conventional cancer therapeutic is at least one of chemotherapy, immunotherapy, hormone ablation or surgery. 
     
     
         24 . A composition comprising one or more tumor cell antigens that elicit an immune response against a tumor and an MFG-E8 inhibitor, wherein the MFG-E8 inhibitor is selected from the group consisting of an anti-MFG-E8 antibody, an anti-phosphatidyl serine antibody, an MFG-E8 polypeptide that lacks the ability to bind integrins; and an MFG-E8 polypeptide that lacks the ability to bind phosphatidyl serine. 
     
     
         25 . The composition of  claim 24 , wherein the composition comprises autologous tumor cells expressing one or more tumor cell antigens. 
     
     
         26 . The composition of  claim 25 , wherein the autologous tumor cells express GM-CSF. 
     
     
         27 . The composition of  claim 25 , wherein the autologous tumor cells harbor recombinant DNA encoding GM-CSF. 
     
     
         28 . The composition of  claim 25  wherein the autologous tumor cells are proliferation incompetent or have been irradiated. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . The composition of  claim 24 , further comprising a GM-CSF expressing cell. 
     
     
         32 . The composition of  claim 31 , wherein the GM-CSF expressing cell secretes GM-CSF. 
     
     
         33 . The composition of  claim 31 , wherein the GM-CSF expressing cell is a cell line engineered to express GM-CSF. 
     
     
         34 . The composition of  claim 31 , wherein the GM-CSF expressing cell harbors recombinant DNA encoding GM-CSF. 
     
     
         35 . The composition of  claim 33  wherein the cell line is K562. 
     
     
         36 . The composition of  claim 31 , wherein the GM-CSF expressing cell is proliferation incompetent or has been irradiated. 
     
     
         37 . (canceled) 
     
     
         38 . The composition of  claim 24 , further comprising GM-CSF. 
     
     
         39 . The composition of  claim 24 , further comprising a pharmaceutically acceptable carrier. 
     
     
         40 . The composition of  claim 24 , further comprising a conventional cancer therapeutic. 
     
     
         41 . The composition of  claim 40 , wherein the conventional cancer therapeutic is an angiogenesis inhibitor. 
     
     
         42 . The composition of  claim 41 , wherein the angiogensis inhibitor inhibits vascular endothelial growth factor (VEGF) activity. 
     
     
         43 . The method  claim 1  further comprising administering antibodies directed against CTLA-4