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 signaling 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 maligancy. In a preferred embodiment is a glioma-specific
immunoreceptor comprising the extracellular targeting domain of the
IL-13R.alpha.2-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.