Chimeric Receptors with 4-1BB Stimulatory Signaling Domain

Abstract

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

What is claimed is: 
     
         1 . A method of enhancing T lymphocyte or natural killer cell activity of an individual by introducing into said individual a T lymphocyte or natural killer cell comprising a chimeric receptor having a cytoplasmic domain comprising the signaling domain of 4-1BB. 
     
     
         2 . A method for treating an individual suffering from cancer by introducing into said individual a T lymphocyte or natural killer cell comprising a chimeric receptor wherein said chimeric receptor comprises an extracellular ligand binding domain, a transmembrane domain, and a cytoplasmic domain, wherein said cytoplasmic domain comprises the signaling domain of 4-1BB. 
     
     
         3 . The method of  claim 2 , wherein the cancer is selected from the group consisting of lung cancer, melanoma, breast cancer, prostate cancer, colon cancer, renal cell carcinoma, ovarian cancer, neuroblastoma, rhabdomyosarcoma, leukemia, and lymphoma. 
     
     
         4 . The method of  claim 2 , wherein the extracellular ligand binding domain comprises a single chain variable domain of an anti-CD19 monoclonal antibody. 
     
     
         5 . The method of  claim 4 , wherein the cancer is of B cell origin. 
     
     
         6 . The method of  claim 5 , wherein the cancer is selected from the group consisting of B-lineage acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia, and B-cell non-Hodgkin's lymphoma.