Generation of cytotoxic tumor specific cell lines and uses thereof

Abstract

An in-vitro method of activating T cells is disclosed. The method comprises incubating T cells with pathogenic cells in the presence of a multimeric peptide comprising at least two peptide monomers linked to one another, each of the at least two peptide monomers comprising at least 6 consecutive amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, wherein the at least two peptide monomers are each no longer than 30 amino acids, wherein the multimeric peptide is capable of reducing binding of PLIF to human leukocytes under conditions which allow expansion of the T cells.

What is claimed is: 
     
         1 . An isolated cytotoxic T cell line which comprises a multimeric peptide attached to an outer surface of T cells of the T cell line, said multimeric peptide comprising at least two peptide monomers linked to one another, each of said at least two peptide monomers comprising at least 6 consecutive amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, wherein said at least two peptide monomers are each no longer than 30 amino acids. 
     
     
         2 . A method of treating a disease which is amenable to treatment by adoptive immunotherapy in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the cytotoxic T cell line of  claim 1 , thereby treating the disease. 
     
     
         3 . The method of  claim 2 , wherein the disease is cancer. 
     
     
         4 . The method of  claim 3 , wherein the cancer of the subject expresses at least one HLA class I allele which is identical to a HLA class I allele expressed on cancer cells used to generate the cytotoxic T cells. 
     
     
         5 . The method of  claim 2 , wherein the cytotoxic T cell line is generated using PBMCs. 
     
     
         6 . The method of  claim 5 , wherein said PBMCs are autologous to the subject. 
     
     
         7 . The method of  claim 3 , wherein the cancer of the subject is selected from the group consisting of breast cancer, colon cancer, lung cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphatic leukemia (ALL) and renal cancer. 
     
     
         8 . The method of  claim 7 , wherein said breast cancer comprises triple negative breast cancer. 
     
     
         9 . The method of  claim 2 , wherein said cytotoxic T cell line is generated by incubating T cells with pathogenic cells in the presence of a multimeric peptide comprising at least two peptide monomers linked to one another, each of said at least two peptide monomers comprising at least 6 consecutive amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, wherein said at least two peptide monomers are each no longer than 30 amino acids, wherein the multimeric peptide is capable of reducing binding of PLIF to human leukocytes under conditions which allow expansion of said T cells. 
     
     
         10 . A bank comprising a plurality of the cytotoxic T cell lines of  claim 1 .