Chimeric immunoreceptor useful in treating human cancers

Abstract

The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin/paracrine cytokine systems utilized by human malignancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targetting domain of the IL-13Rα2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

1 . A chimeric immunoreceptor comprising SEQ ID NO:22. 
     
     
         2 . A chimeric immunoreceptor encoded by a nucleic acid sequence comprising SEQ ID NO:19 or SEQ ID NO:23. 
     
     
         3 . A method for treating human cancer, comprising administering to a human suffering from a glioma that overexpresses IL13α2 receptor a plurality of T lymphocyte cells expressing an immunoreceptor of  claim 1  or  claim 2 . 
     
     
         4 . A vector which comprises a nucleic acid comprising SEQ ID NO: 19 or SEQ ID NO:23. 
     
     
         5 . The vector which consists essentially of SEQ ID NO:19. 
     
     
         6 . The vector which consists essentially of SEQ ID NO:23.