Compositions and methods of muscle specific kinase chimeric autoantibody receptor cells
AssigneeThe Trustees of the University of Pennsylvania
InventorsAimee S. Payne, Christoph T. Ellebrecht, Sangwook Oh, Michael C. Milone
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Abstract
The invention includes a chimeric autoantibody receptor (CAAR) specific for anti-muscle-specific kinase (MuSK) B cell receptor (BCR), compositions comprising the CAAR, polynucleotides encoding the CAAR, vectors comprising a polynucleotide encoding the CAAR, and recombinant cells comprising the CAAR.
Claims17
A genetically modified cell comprising a chimeric autoantibody receptor (CAAR), wherein the CAAR comprises:
- (i) an extracellular domain comprising a muscle-specific kinase (MuSK) autoantigen comprising the amino acid sequence of SEQ ID NO:
- 11 or 23,
- (ii) a CD8 alpha transmembrane domain comprising the amino acid sequence of SEQ ID NO:
- 13,
- (iii) a 4-1BB intracellular domain comprising the amino acid sequence of SEQ ID NO:
- 14, and
- (iv) a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 15.
A method for treating an autoantibody-mediated neuromuscular junction (NMJ) disease in a subject, the method comprising:
- administering to the subject an effective amount of a genetically modified cell comprising a polynucleotide encoding a chimeric autoantibody receptor (CAAR), wherein the CAAR comprises:
- (i) an extracellular domain comprising a muscle-specific kinase (MuSK) autoantigen comprising the amino acid sequence of SEQ ID NO:
- 11 or 23,
- (ii) a CD8 alpha transmembrane domain comprising the amino acid sequence of SEQ ID NO:
- 13,
- (iii) a 4-1BB intracellular domain comprising the amino acid sequence of SEQ ID NO:
- 14, and
- (iv) a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 15,
- thereby treating the autoantibody-mediated NMJ disease in the subject, wherein the autoantibody-mediated NMJ disease is myasthenia gravis.
A method for preventing or reducing neuromuscular junction (NMJ) damage in a subject at risk of or suffering from an autoantibody-mediated NMJ disease, the method comprising:
- administering to the subject an effective amount of a genetically modified cell comprising a polynucleotide encoding a chimeric autoantibody receptor (CAAR), wherein the CAAR comprises:
- (i) an extracellular domain comprising a muscle-specific kinase (MuSK) autoantigen comprising the amino acid sequence of SEQ ID NO:
- 11 or 23,
- (ii) a CD8 alpha transmembrane domain comprising the amino acid sequence of SEQ ID NO:
- 13,
- (iii) a 4-1BB intracellular domain comprising the amino acid sequence of SEQ ID NO:
- 14, and
- (iv) a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 15,
- thereby preventing or reducing NMJ damage in the subject, wherein the autoantibody-mediated NMJ disease is myasthenia gravis.
Dependencies are inferred from the claim text.