Treatment of cancer using a CD33 chimeric antigen receptor
AssigneesNovartis AG, The Trustees of the University of Pennsylvania
InventorsHilmar Erhard Ebersbach, Thomas Huber, Julia Jascur, Celeste Richardson, Reshma Singh, Huijuan Song, Qilong Wu, Jiquan Zhang
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Abstract
The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.
Claims22
An isolated chimeric antigen receptor (CAR) polypeptide, wherein the CAR comprises a CD33 binding domain, a transmembrane domain, and an intracellular signaling domain comprising a costimulatory domain, a primary signaling domain, or both a costimulatory domain and a primary signaling domain, and wherein said CD33 binding domain comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:
- (i) a heavy chain variable region comprising:
- a heavy chain complementary determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO:
- 274, a heavy chain complementary determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO:
- 283, and a heavy chain complementary determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:292 present in order of HC CDR1, HC CDR2, and HC CDR3;
- and
- a light chain variable region comprising:
- a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO:
- 301, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO:
- 310, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:319 present in order of LC CDR1, LC CDR2, and LC CDR3;
- (ii) a heavy chain variable region comprising:
- a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO:
- 328, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO:
- 337, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:346 present in order of HC CDR1, HC CDR2, and HC CDR3;
- and
- a light chain variable region comprising:
- a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO:
- 355, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO:
- 364, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:373 present in order of LC CDR1, LC CDR2, and LC CDR3;
- and
- (iii) a heavy chain variable region comprising:
- a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO:
- 89, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO:
- 98, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:107, present in order of HC CDR1, HC CDR2, and HC CDR3;
- and
- a light chain variable region comprising:
- a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO:
- 116, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO:
- 125, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:134 present in order of LC CDR1, LC CDR2, and LC CDR3.
Dependencies are inferred from the claim text.