CE7-specific redirected immune cells
Genetically engineered, CE7-specific redirected immune cells expressing a cell surface protein having an extracellular domain comprising a receptor which is specific for CE7, an intracellular signaling domain, and a transmembrane domain, and methods of use for such cells for cellular immunotherapy of CE7+ neuroblastoma are disclosed. In one embodiment, the immune cell is a T cell and the cell surface protein is a single chain FvFc:ζ receptor where Fv designates the V H and V L chains of a single chain monoclonal antibody to CE7 linked by peptide, Fc represents a hinge —C H 2—C H 3 region of a human IgG 1 , and ζ represents the intracellular signaling domain of the zeta chain of human CD3. DNA constructs encoding a chimeric T-cell receptor and a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor are also disclosed.
1. Genetically engineered human CE7-specific T cells which express and bear on the cell surface membrane a CE7-specific chimeric receptor comprising at least one intracellular signaling domain, at least one transmembrane domain and at least one extracellular domain, wherein the extracellular domain comprises a CE7-specific receptor and wherein the CE7-specific chimeric receptor comprises amino acids 21–631 of SEQ ID NO:2.
2. The CE7-specific T cells of claim 1 which are CD4 + and which produce IL-2 when co-cultured in vitro with CE7 + neuroblastoma cells.
3. The CE7-specific T cells of claim 1 which are CD8 + and which lyse CE7 + neuroblastoma target cells when co-cultured in vitro with the target cells.
4. The CE7-specific T cells of claim 1 which comprise a mixed population of CD4 + and CD8 + cells.