CD28 compositions and methods for chimeric antigen receptor therapy
AssigneesNovartis AG, The Trustees of the University of Pennsylvania
InventorsAvery D. Posey, Sonia Guedan Carrio
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Abstract
The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein. The CAR may comprise a mutant CD28 costimulatory domain.
Claims12
A chimeric antigen receptor (CAR) molecule comprising:
- i) an antigen binding domain,
- ii) a transmembrane domain, and
- iii) an intracellular domain that comprises a costimulatory domain that comprises the amino acid sequence of RSKRSRLLHSDX1MX2MTPRRPGPTRKHYQPYAPPRDFAAYRS (SEQ ID NO:
- 1), a sequence at least 95% identical thereto, or a sequence with no more than 1, 2, 3, or 4 modifications of SEQ ID NO:
- 1 and wherein
- X1 is any amino acid, and
- X2 is selected from R (Arg), C (Cys), E (Glu), G (Gly), H (His), I (Ile), L (Leu), M (Met), F (Phe), S (Ser), T (Thr), W (Trp), Y (Tyr), or V (Val),
- provided that SEQ ID NO:
- 1 is not RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS (SEQ ID NO:
- 5).
A chimeric antigen receptor (CAR) molecule comprising:
- i) an antigen binding domain,
- ii) a transmembrane domain, and
- iii) an intracellular domain that comprises a costimulatory domain that comprises the amino acid sequence of RSKRSRLLHSDYMFMTPRRPGPTRKHYQPYAPPRDFAAYRS (SEQ ID NO:
- 2, wherein the intracellular domain further comprises a primary signaling domain.
Dependencies are inferred from the claim text.