US 5,359,046 AGranted

Chimeric chains for receptor-associated signal transduction pathways

AssigneesCell Genesys, Inc., The Regents of the University of California

InventorsDaniel J. Capon, Arthur Weiss, Brian A. Irving, Margo R. Roberts, Krisztina Zsebo

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Abstract

Chimeric proteins and DNA sequence encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA sequences may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Claims21

Dependent claims

Chimeric DNA sequence encoding a membrane bond protein, said chimeric DNA comprising in reading frame:

a DNA sequence encoding a signal sequence which directs the membrane bound protein to the surface membrane;
a DNA sequence encoding a non-MHC restricted extracellular binding domain of a surface membrane protein selected from the group consisting of CD4, CD8, immunoglobulin and single-chain antibody that binds specifically to at least one ligand, wherein said ligand is a protein on the surface of a cell or a viral protein;
a transmbembrane domain from a protein selected from the group consisting of CD4, CD8, immunoglobulin, single-chain antibody, the CD3 zeta chain, the CD3 gamma chain, the CD3 delta chain and the CD3 epsilon chain;
and
a cytoplasmic signal-transducing domain of a protein that activates an intracellular messenger system selected from the group consisting of the CD3 zeta chain, the CD3 gamma chain, the CD3 delta chain and the CD3 epsilon chain,
wherein said extracellular domain and cytoplasmic domain are not naturally joined together and said cytoplasmic domain is not naturally joined to an extracellular ligand-binding domain, and when said chimeric DNA is expressed as a membrane bound protein in a selected host cell under conditions suitable for expression, said membrane bond protein initiates signalling in said host cell.

3 more elements

Dependencies are inferred from the claim text.