Chimeric receptor with NKG2D specificity for use in cell therapy against cancer and infectious disease
AssigneesSt. Jude Children's Research Hospital, National University of Singapore
InventorsDario Campana, Yu-Hsiang Chang
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Abstract
The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases.
Claims19
A chimeric receptor complex, comprising:
- a first polypeptide comprising a Natural killer Group 2 member D (NKG2D) receptor extracellular ligand-binding domain and a CD3zeta signaling domain,
- wherein the NKG2D receptor extracellular ligand-binding domain has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 12,
- wherein the CD3zeta signaling domain has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 10;
- and
- a second polypeptide comprising a DNAX-activating protein 10 (DAP10) stimulatory molecule,
- wherein the DAP10 stimulatory molecule has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 14.
A chimeric receptor complex, comprising:
- a first polypeptide comprising a Natural killer Group 2 member D (NKG2D) receptor extracellular ligand-binding domain and a CD3zeta signaling domain,
- wherein the NKG2D receptor extracellular ligand-binding domain comprises the amino acid sequence of SEQ ID NO:
- 12,
- wherein the CD3zeta signaling domain has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 10;
- and
- a second polypeptide comprising a DNAX-activating protein 10 (DAP10) stimulatory molecule,
- wherein the DAP10 stimulatory molecule comprises the amino acid sequence of SEQ ID NO:
- 14.
A chimeric receptor complex, comprising:
- a first polypeptide comprising a Natural killer Group 2 member D (NKG2D) receptor extracellular ligand-binding domain and a CD3zeta signaling domain,
- wherein the NKG2D receptor extracellular ligand-binding domain comprises the amino acid sequence of SEQ ID NO:
- 12,
- wherein the CD3zeta signaling domain has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:
- 10;
- and
- a second polypeptide comprising a DNAX-activating protein 10 (DAP10) stimulatory molecule,
- wherein the DAP10 stimulatory molecule has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:
- 14.
Dependencies are inferred from the claim text.