CE7-specific redirected immune cells

• US 7,070,995 B2
• Filed: 04/11/2002
• Issued: 07/04/2006
• Est. Priority Date: 04/11/2001
• Status: Active Grant

• Current Assignee: City of Hope
• Original Assignee: City of Hope
• Inventors: Jensen, Michael
• Primary Examiner(s): Siew, Jeffrey
• Assistant Examiner(s): Blanchard, David J.
• Application Number:
  US10/120,198
• Publication Number:
  US 20030215427A1
• Time in Patent Office: 1,545 Days
• Field of Search: 435/325, 435/326, 435/328, 435/329, 435/332, 435/343, 435/344, 536/23.1
• US Class Current: 435/372.3
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/03 containing a transmembrane segment
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

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_H2—C_H3 region of a human IgG₁, 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.

Claims

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.