Compositions and methods of NKG2D chimeric antigen receptor T cells for controlling triple-negative breast cancer
AssigneeThe Trustees of the University of Pennsylvania
InventorsDaniel Powell, De-Gang Song
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Abstract
The invention includes a chimeric antigen receptor (CAR) specific for a natural-killer group 2, member D ligand (NKG2DL), compositions comprising the CAR, polynucleotides encoding the CAR, vectors comprising a polynucleotide encoding the CAR, and recombinant T cells comprising the CAR. The invention also includes methods of making a genetically modified T cell expressing a NKG2D-CAR wherein the expressed CAR comprises a NKG2D extracellular domain. The present invention also relates generally to the use of T cells engineered to express a CAR to treat cancer associated with NKG2D.
Claims15
A nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein the nucleic acid molecule comprises a nucleic acid sequence encoding a natural-killer group 2, member D (NKG2D) extracellular domain, a nucleic acid sequence encoding a CD27 costimulatory domain, and a nucleic acid sequence encoding a CD3 zeta signaling domain,
- wherein the CAR comprises, from amino to carboxy terminus, the NKG2D extracellular domain, the CD27 costimulatory domain, and the CD3 zeta signaling domain, and
- wherein the CAR comprises the amino acid sequence of SEQ ID NO:
- 15.
A chimeric antigen receptor (CAR) comprising a natural-killer group 2, member D (NKG2D) extracellular domain, a CD27 costimulatory domain, and a CD3 zeta signaling domain,
- wherein the CAR comprises, from amino to carboxy terminus, the NKG2D extracellular domain, the CD27 costimulatory domain, and the CD3 zeta signaling domain, and
- wherein the CAR comprises the amino acid sequence of SEQ ID NO:
- 15.
A genetically modified T cell comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein the nucleic acid molecule comprises a nucleic acid sequence encoding, from amino to carboxy terminus, a natural-killer group 2, member D (NKG2D) extracellular domain, a nucleic acid sequence encoding a CD27 costimulatory domain, and a nucleic acid sequence encoding a CD3 zeta signaling domain,
- wherein the CAR comprises the amino acid sequence of SEQ ID NO:
- 15 or is encoded by the nucleic acid sequence of SEQ ID NO:
- 14.
A genetically modified T cell comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO:
- 16 or encodes the amino acid sequence of SEQ ID NO:
- 17.
A genetically modified T cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises the amino acid sequence of SEQ ID NO:
- 19 or is encoded by the nucleic acid sequence of SEQ ID NO:
- 18.
A vector comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein the nucleic acid molecule comprises a nucleic acid sequence encoding, from amino to carboxy terminus, a natural-killer group 2, member D (NKG2D) extracellular domain, a nucleic acid sequence encoding a CD27 costimulatory domain, and a nucleic acid sequence encoding a CD3 zeta signaling domain,
- wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO:
- 1.
A method for treating triple negative breast cancer (TNBC) in a subject, the method comprising:
- administering to the subject an effective amount of a genetically modified T cell comprising a nucleic acid molecule encoding, from amino to carboxy terminus, a chimeric antigen receptor (CAR), wherein the nucleic acid molecule comprises a nucleic acid sequence of a natural-killer group 2, member D (NKG2D) extracellular domain, a nucleic acid sequence encoding a CD27 costimulatory domain, and a nucleic acid sequence encoding a CD3 zeta signaling domain, thereby treating TNBC in the subject.
Dependencies are inferred from the claim text.