The present invention relates to chimeric transmembrane immunoreceptors, named"zetakines", comprised of an extracellular domain comprising a solublereceptor ligand linked to a support region capable of tethering theextracellular domain to a cell surface, a transmembrane region and anintracellular signalling domain. Zetakines, when expressed on the surface of Tlymphocytes, direct T cell activity to those specific cells expressing areceptor for which the soluble receptor ligand is specific. Zetakine chimericimmunoreceptors represent a novel extension of antibody-based immunoreceptorsfor redirecting the antigen specificity of T cells, with application totreatment of a variety of cancers, particularly via the autocrin/paracrinecytokine systems utilized by human maligancy. In a preferred embodiment is aglioma-specific immunoreceptor comprising the extracellular targetting domainof the IL-13R.alpha.2-specific IL-13 mutant IL-13(E13Y) linked to the Fcregion of IgG, the transmembrane domain of human CD4, and the human CD3 zetachain.
