Therapeutic and diagnostic cloned mhc-unrestricted receptor specific for the muc1 tumor associated antigen

Abstract

The invention provides an isolated nucleic acid encoding a receptor, other than an immunoglobulin, wherein the receptor binds to a MUC1 tumor antigen independently of an major histocompatibility complex (MHC). The invention provides a method of activating a signaling pathway and/or killing a cancer cell using a receptor that is similar to or is a T cell receptor

1 - 49 . (canceled) 
     
     
         50 . An isolated or substantially purified receptor other than an immunoglobulin, wherein the receptor binds to a MUC1 tumor antigen independently of a major histocompatibility complex (MHC). 
     
     
         51 . The isolated or substantially purified receptor of  claim 50 , wherein the receptor is soluble. 
     
     
         52 . The isolated or substantially purified receptor of  claim 50 , wherein the receptor is membrane bound. 
     
     
         53 . An immunocytochemistry stain comprising a receptor, other than an immunoglobulin, wherein the receptor binds to a MUC1 tumor antigen independently of a major histocompatibility complex (MHC), complexed with a labeling agent. 
     
     
         54 . The immunocytochemistry stain of  claim 53 , wherein the receptor is soluble. 
     
     
         55 . The immunocytochemistry stain of  claim 53 , wherein the receptor is membrane bound. 
     
     
         56 . (canceled) 
     
     
         57 . A method of activating a signaling pathway in a cell having a signaling pathway, the method comprising:
 a. transducing the cell having a signaling pathway with at least one nucleic acid encoding a receptor, wherein the receptor
 i. is expressed and displayed on the surface of the transduced cell, 
 ii. binds to a MUC1 tumor antigen independently of a major histocompatibility complex (MHC), and 
   b. contacting the transduced cell to a cell expressing the MUC1 tumor antigen thereby activating the signaling pathway.   
     
     
         58 . The method of  claim 57 , wherein the receptor is a T cell receptor. 
     
     
         59 . (canceled) 
     
     
         60 . (canceled) 
     
     
         61 . A method of activating a signaling pathway in a cell comprising a signaling pathway, the method comprising transducing the cell with a receptor having affinity for MUC1, wherein the affinity is determined by a first amino acid sequence and a second amino acid sequence, wherein
 the first amino acid sequence consists essentially of the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   the second amino acid sequence consists essentially of the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         62 . A method of killing a cancer cell, the method comprising
 a. isolating a population of cells comprising a receptor, wherein the receptor binds to a MUC1 tumor antigen independently of a major histocompatibility complex (MHC), and   b. contacting the isolated population of cells to a cell expressing the MUC1 tumor antigen thereby killing the cancer cell.   
     
     
         63 . The method of  claim 62 , wherein the population comprises T cells. 
     
     
         64 . The method of  claim 62 , wherein the population consists essentially of T cells. 
     
     
         65 . The method of  claim 62 , wherein the population does not comprise cells, other than T cells, that comprise a receptor that binds to a MUC1 tumor antigen independently of a major histocompatibility complex (MHC). 
     
     
         66 . The isolated or substantially purified receptor of  claim 50 , wherein the receptor:
 a. has a first amino acid sequence that is identical with the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that is identical with the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         67 . The isolated or substantially purified receptor of  claim 50 , wherein the receptor:
 a. has a first amino acid sequence that consists essentially of the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that consists essentially of the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         68 . The immunocytochemistry stain of  claim 53 , wherein the receptor:
 a. has a first amino acid sequence that is identical with the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that is identical with the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         69 . The immunocytochemistry stain of  claim 53 , wherein the receptor:
 a. has a first amino acid sequence that consists essentially of the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that consists essentially of the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         70 . The method of  claim 57 , wherein the receptor:
 a. has a first amino acid sequence that is identical with the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that is identical with the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         71 . The method of  claim 57 , wherein the receptor:
 a. has a first amino acid sequence that consists essentially of the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that consists essentially of the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         72 . The method of  claim 62 , wherein the receptor:
 a. has a first amino acid sequence that is identical with the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that is identical with the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).   
     
     
         73 . The method of  claim 62 , wherein the receptor:
 a. has a first amino acid sequence that consists essentially of the portion of MA Vα23 shown in  FIG. 1  (SEQ ID NO:1), and   b. has a second amino acid sequence that consists essentially of the portion of MA Vβ8.3 shown in  FIG. 1  (SEQ ID NO:2).