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.