Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor
AssigneesNovartis AG, The Trustees of the University of Pennsylvania, University of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsJennifer Brogdon, Laura Alexandra Johnson, Carl H. June, Andreas Loew, Marcela Maus, John Scholler, Hideho Okada
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Abstract
The invention provides compositions and methods for treating diseases associated with expression of EGFRvIII. The invention also relates to chimeric antigen receptor (CAR) specific to EGFRvIII, vectors encoding the same, and recombinant T cells comprising the anti-EGFRvIII CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an anti-EGFRvIII binding domain.
Claims38
An isolated nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein said CAR comprises an anti-EGFRvIII binding domain, a transmembrane domain, and an intracellular signaling domain comprising a primary signaling domain, a costimulatory domain, or both a primary signaling domain and a costimulatory domain, wherein the encoded anti-EGFRvIII binding domain comprises an amino acid sequence with greater than 99% sequence identity to SEQ ID NO:68 comprising:
- (a) a heavy chain immunoglobulin variable region comprising:
- (i) a CDR1 comprising the sequence DYYIH (SEQ ID NO:
- 22);
- (ii) a CDR2 comprising the sequence RIDPENDETKYGPIFQG (SEQ ID NO:
- 23);
- and
- (iii) a CDR3 comprising the sequence RGGVY (SEQ ID NO:
- 24);
- and
- (b) a light chain immunoglobulin variable region comprising:
- (i) a CDR1 comprising the sequence KSSQSLLDSDGKTYLN (SEQ ID NO:
- 26);
- (ii) a CDR2 comprising the sequence LVSKLDS (SEQ ID NO:
- 27);
- and
- (iii) a CDR3 comprising the sequence WQGTHFPGT (SEQ ID NO:
- 28).
Dependencies are inferred from the claim text.