Chimeric receptors and methods of use thereof
AssigneeSenti Biosciences, Inc.
InventorsBrian Scott Garrison, Jennifer Chien, Kathryn Armstrong Loving, Russell Morrison Gordley, Michelle Elizabeth Hung
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Abstract
Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.
Claims28
A method of treating a subject having acute myeloid leukemia (AML), wherein the method comprises delivering to the subject an autologous or an allogeneic T cell or Natural Killer (NK) cell comprising:
- (a) an anti-FLT3 chimeric antigen receptor (CAR) comprising a FLT3-binding domain and an anti-CD33 CAR comprising a CD33-binding domain, or a bivalent CAR comprising a FLT3-binding domain and a CD33-binding domain,
- wherein the FLT3-binding domain comprises a heavy chain variable domain (VH) comprising a CDR-H1 sequence comprising the amino acid sequence of SEQ ID NO:
- 81, a CDR-H2 sequence comprising the amino acid sequence of SEQ ID NO:
- 82, and a CDR-H3 sequence comprising the amino acid sequence of SEQ ID NO:
- 83 and a light chain variable domain (VL) comprising a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO:
- 84, a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO:
- 85, and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO:
- 86, and
- wherein the CD33-binding domain comprises VH comprising a CDR-H1 sequence comprising the amino acid sequence of SEQ ID NO:
- 123, a CDR-H2 sequence comprising the amino acid sequence of SEQ ID NO:
- 124, and a CDR-H3 sequence comprising the amino acid sequence of SEQ ID NO:
- 125 and a VL comprising a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO:
- 126, a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO:
- 127, and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO:
- 128;
- and
- (b) an inhibitory chimeric receptor comprising an extracellular antigen-binding domain that binds to EMCN.
A method of providing an anti-tumor immunity in a subject, wherein the anti-tumor immunity comprises targeting AML, the method comprising administering to the subject in need thereof a therapeutically effective dose of an autologous or an allogeneic T cell or NK cell comprising:
- (a) an anti-FLT3 CAR comprising a FLT3-binding domain and an anti-CD33 CAR comprising a CD33-binding domain, or a bivalent CAR comprising a FLT3-binding domain and a CD33-binding domain,
- wherein the FLT3-binding domain comprises a VH comprising a CDR-H1 sequence comprising the amino acid sequence of SEQ ID NO:
- 81, a CDR-H2 sequence comprising the amino acid sequence of SEQ ID NO:
- 82, and a CDR-H3 sequence comprising the amino acid sequence of SEQ ID NO:
- 83 and a VL comprising a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO:
- 84, a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO:
- 85, and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO:
- 86, and
- wherein the CD33-binding domain comprises a VH comprising a CDR-H1 sequence comprising the amino acid sequence of SEQ ID NO:
- 123, a CDR-H2 sequence comprising the amino acid sequence of SEQ ID NO:
- 124, and a CDR-H3 sequence comprising the amino acid sequence of SEQ ID NO:
- 125 and a VL comprising a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO:
- 126, a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO:
- 127, and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO:
- 128;
- and
- (b) an inhibitory chimeric receptor comprising an extracellular antigen-binding domain that binds to EMCN.
Dependencies are inferred from the claim text.