Compositions and methods of using crmp-1 and its fragments for treating cancer

Abstract

Active fragments of hcrmp1 that are capable of inhibiting cell proliferation, invasive activity, and metastasis of cancer and methods of using the same for treating cancer are disclosed. The method can also be used prior to, or in combination with, the administration a chemotherapy agent. Vectors capable of expressing an hcrmp1, variants of hcrmp1, fragments of hcrmp1 and/or variants of fragments of hcrmp1 are also disclosed.

1 . An isolated polypeptide, which is a fragment of CRMP-1 protein that comprises the amino acid sequence of SEQ ID NO: 1, wherein the isolated polypeptide has no longer than 500 amino acid residues in length and is active in inhibiting the proliferation, metastasis, and/or invasion of a cancer cell. 
     
     
         2 . An isolated polypeptide according to  claim 1 , comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 15, 17, 19, 21, 23, 25, and 39-43. 
     
     
         3 . The isolated polypeptide of  claim 2 , wherein the polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 17 and 39. 
     
     
         4 . An isolated polypeptide according to  claim 1 , the amino acid sequence of which is selected from the group consisting of SEQ ID NOs: 15, 17, 19, 21, 23, 25, and 39-43. 
     
     
         5 . An isolated polypeptide according to  claim 1 , the amino acid sequence of which is selected from the group consisting of SEQ ID NOs: 17 and 39. 
     
     
         6 . An isolated polypeptide according to  claim 1 , which is encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 16, 18, 20, 22, 24, 26 and 33-38. 
     
     
         7 . An isolated polypeptide according to  claim 1 , which is encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 18 and 34. 
     
     
         8 . A method of making the isolated polypeptide of  claim 1 , comprising the step of:
 (a) constructing a recombinant vector comprising:
 (i) at least one regulatory element; and 
 (ii) a nucleic acid insert encoding the isolated polypeptide, comprising the nucleotide sequence selected from the group consisting of SEQ ID NOs: 16, 18, 20, 22, 24, 26, 33, 34, 35, 36, 37, and 38, linked in translation frame to the at least one regulatory element; 
   wherein the vector does not fully encode SEQ ID NO:1, and wherein the isolated polypeptide has no longer than 500 amino acid residues in length and is active in inhibiting the proliferation, metastasis, and/or invasion of a cancer cell; and   (b) transfecting a host cell with the recombinant vector from step (a); and   (c) inducing the expression of the nucleic acid insert in the host cell to obtain the isolated polypeptide.   
     
     
         9 . A fusion protein consisting of:
 (a) a protein transduction domain (PTD); and   (b) an isolated polypeptide according to  claim 1 , operably linked to the PTD.   
     
     
         10 . A fusion protein consisting of:
 (a) a protein transduction domain (PTD); and   (b) an isolated polypeptide according to  claim 3 , operably linked to the PTD.   
     
     
         11 . A fusion protein consisting of:
 (a) a protein transduction domain (PTD); and   (b) an isolated polypeptide according to  claim 5 , operably linked to the PTD.   
     
     
         12 . A composition comprising a therapeutically effective amount of an isolated polypeptide according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . A composition comprising a therapeutically effective amount of an isolated polypeptide according to  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         14 . A composition comprising a therapeutically effective amount of an isolated polypeptide according to  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         15 . A composition comprising a therapeutically effective amount of an isolated polypeptide according to  claim 4  and a pharmaceutically acceptable carrier. 
     
     
         16 . A composition comprising a therapeutically effective amount of an isolated polypeptide according to  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         17 . A composition comprising a therapeutically effective amount of an isolated polypeptide according to  claim 6  and a pharmaceutically acceptable carrier. 
     
     
         18 . A method of inhibiting the proliferation, metastasis, and/or invasion of a cancer cell in a patient in need thereof, comprising the step of administering an effective amount of the composition of  claim 12 . 
     
     
         19 . A method of inhibiting the proliferation, metastasis, and/or invasion of a cancer cell in a patient in need thereof, comprising the step of administering an effective amount of the composition of  claim 14 . 
     
     
         20 . A method of inhibiting the proliferation, metastasis, and/or invasion of a cancer cell in a patient in need thereof, comprising the step of administering an effective amount of the composition of  claim 16 .