Tumor therapy

Abstract

Neoplasia is treated by administering to a mammalian host a composition comprising ligands for the NKG2D receptor. In addition, other NKG2D ligands, proteins specific for the neoplastic cells and cytokines may be included to enhance the immune response. The composition may be cells comprising expression constructs for the ligands, liposomes or combinations of protein molecules.

1. A method for inhibiting prostate tumor growth in a mammalian host determined to have a metastatic prostate tumor and comprising prostate tumor cells expressing native NKG2D, the method comprising steps:
 administering to the mammalian host a host-compatible cell transduced to express on the surface of the cell a plurality of NKG2D-binding moieties of natural NKG2D ligands selected from the group consisting of MICA, MICB and ULBP, wherein the administering step is effective to inhibit growth of the tumor; and detecting a resultant inhibition of growth of the tumor by evaluating growth of the tumor.  
 
     
     
       2. The method of  claim 1 , wherein the host-compatible cell is derived from the tumor. 
     
     
       3. A method for inhibiting primary mammary tumor growth in a mammalian host determined to have a primary mammary tumor and comprising mammary tumor cells expressing native NKG2D, the method comprising steps:
 administering to the mammalian host a host-compatible cell transduced to express on the surface of the cell a plurality of A  NKG2D-binding moieties of natural NKG2D ligands selected from the group consisting of MICA, MICB and ULBP, wherein the administering step is effective to inhibit growth of the tumor; and  
 detecting a resultant inhibition of growth of the tumor by evaluating growth of the tumor.  
 
     
     
       4. The method of  claim 3 , wherein the host-compatible cell is derived from the tumor. 
     
     
       5. A method for inhibiting tumor growth in a mammalian host determined to have a tumor arising in situ and comprising tumor cells expressing native NKG 2 D, the method comprising steps:
 administering to the mammalian host a composition comprising a multivalent NKG 2 D-binding agent, wherein the administering step is effective to inhibit growth of the tumor; and    detecting a resultant inhibition of growth of the tumor.   
     
     
       6. The method of  claim 5 , wherein the tumor cells express a detectable amount of a native NKG 2 D ligand. 
     
     
       7. The method of  claim 5 , wherein the tumor cells express a substantially undetectable amount of native NKG 2 D ligand. 
     
     
       8. The method of  claim 5 , wherein the tumor cells are melanoma cells. 
     
     
       9. The method of  claim 5 , wherein the tumor cells present downregulated MHC class I proteins. 
     
     
       10. The method of  claim 5 , wherein the tumor cells are substantially non-immunogenic in the mammalian host. 
     
     
       11. The method of  claim 5 , wherein the tumor cells are highly metastatic. 
     
     
       12. The method of  claim 5 , wherein the tumor cells are highly tumorigenic. 
     
     
       13. The method of  claim 5 , wherein the administering is remote from the tumor. 
     
     
       14. The method of  claim 5 , wherein the agent comprises a NKG 2 D-specific antibody. 
     
     
       15. The method of  claim 5 , wherein the agent comprises a NKG 2 D ligand comprising a plurality of covalently linked natural NKG 2 D binding moieties. 
     
     
       16. The method of  claim 5 , wherein the agent comprises a NKG 2 D ligand comprising a plurality of non-covalently linked natural NKG 2 D binding moieties, wherein the moieties are restricted to a common presenting surface. 
     
     
       17. The method of  claim 5 , wherein the agent comprises a NKG 2 D ligand comprising a plurality of non-covalently linked natural NKG 2 D binding moieties, wherein the moieties are restricted to a common presenting surface, wherein the common presenting surface is of a host-compatible cell transformed to express the binding moieties. 
     
     
       18. The method of  claim 5 , wherein the agent comprises a NKG 2 D ligand comprising a plurality of non-covalently linked natural NKG 2 D binding moieties, wherein the moieties are restricted to a common presenting surface, wherein the common presenting surface is of a host-compatible cell transformed to express the binding moieties, wherein one or more of the binding moieties are selected from the group consisting of MICA, MICB and ULBP ligand moieties. 
     
     
       19. The method of  claim 5 , wherein the agent comprises a multivalent NKG 2 D ligand comprising a plurality of non-covalently linked natural NKG 2 D ligand moieties, wherein the moieties are restricted to a common presenting surface, wherein the common presenting surface is of a host-compatible cell transformed to express the binding moieties, wherein the cell is derived from the tumor. 
     
     
       20. The method of  claim 5 , wherein the agent comprises a multivalent NKG 2 D ligand comprising a plurality of natural NKG 2 D ligand moieties, wherein one or more of the moieties are selected from the group consisting of MICA, MICB and ULBP ligand moieties. 
     
     
       21. The method of  claim 5 , wherein the agent comprises a NKG 2 D ligand comprising a plurality of non-covalently linked natural NKG 2 D binding moieties, wherein the moieties are restricted to a common presenting surface, wherein the common presenting surface is of a host-compatible cell transformed to express the binding moieties, wherein one or more of the binding moieties are selected from the group consisting of MICA, MICB and ULBP ligand moieties, wherein the cell is derived from the tumor.