Enhancing the t-cell stimulatory capacity of human antigen presenting cells in vitro and in vivo and its use in vaccination

Abstract

We provide new methods of in vitro or in vivo enhancing the T-cell stimulatory capacity of human DCs and the use thereof in cancer vaccination. The method includes the introduction of different molecular adjuvants to human DCs by contacting or modifying them with mRNA or DNA molecule(s) encoding CD40L, and CD70 or constitutively active TILR4 (caTLR4).

What is claimed is: 
     
         1 . A method for the treatment of cancer, comprising intranodal administering to a subject in need thereof:
 one or more isolated mRNA molecule(s) encoding for:
 a functional immunostimulatory protein CD40L, constitutively active TLR4 (caTLR4), and a functional immunostimulatory protein CD70; and 
   one or more tumor antigens
 wherein said method does not include the administration of dendritic cells to said subject. 
   
     
     
         2 . The method according to  claim 1 , wherein said one or more tumor antigens are administered before, after, or simultaneously with the one or more isolated mRNA molecule(s). 
     
     
         3 . The method of  claim 1 , wherein said one or more tumor antigen is selected from the group consisting of: total mRNA isolated from (a) target cell(s), one or more tumor-specific target mRNA molecules, protein lysates of (a) target cell(s), specific proteins from (a) target cell(s), a synthetic tumor-specific peptide or protein, and synthetic mRNA or DNA encoding a tumor-specific antigen or its derived peptide(s). 
     
     
         4 . The method of  claim 1 , additionally comprising administration of mRNA or DNA encoding one or more of the following molecules: IL-12p70, EL-selectin, CCR7, or 4-1BBL. 
     
     
         5 . The method according to  claim 1 , wherein said one or more isolated mRNA molecule(s) encoding the immunostimulatory proteins are part of a single mRNA molecule. 
     
     
         6 . The method according to  claim 5 , wherein the single mRNA molecule is capable of expressing the two or more proteins simultaneously. 
     
     
         7 . The method according to  claim 1 , wherein said mRNA is protected. 
     
     
         8 . The method according to  claim 1 , wherein the cancer is chosen from leukemia, non-small cell lung cancer, small cell lung cancer, CNS cancer, melanoma, ovarian cancer, kidney cancer, prostate cancer, breast cancer, glioma, colon cancer, bladder cancer, sarcoma, pancreatic cancer, colorectal cancer, head and neck cancer, liver cancer, bone cancer, bone marrow cancer, stomach cancer, duodenum cancer, oesophageal cancer, thyroid cancer, hematological cancer, and lymphoma.