Systems targeting PSMA and CA9
AssigneeArsenal Biosciences, Inc.
InventorsAngela Boroughs, Levi Gray-Rupp, Samuel A. Williams, Zhen Jian Zhou, Matthew Drever, Duy Nguyen, Amy-Jo Casbon, Anzhi Yao, Thomas Gardner
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Abstract
Provided herein are antibodies and chimeric priming receptors that bind PSMA and antibodies and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.
Claims61
One or more nucleic acid(s) encoding a system comprising:
- a. a first chimeric polypeptide comprising a priming receptor comprising a first extracellular antigen-binding domain that specifically binds Prostate-Specific Membrane Antigen (PSMA), wherein the first antigen-binding domain comprises a first variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequence set forth in SEQ ID NO:
- 118, and a first variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequence set forth in SEQ ID NO:
- 119;
- and
- b. a second chimeric polypeptide comprising a chimeric antigen receptor (CAR) comprising a second extracellular antigen-binding domain that specifically binds to Carbonic Anhydrase IX (CA9), wherein the second antigen-binding domain comprises a second variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequence set forth in SEQ ID NO:
- 99, and a second variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequence set forth in SEQ ID NO:
- 100.
One or more nucleic acid(s) encoding a system comprising:
- i. a first chimeric polypeptide comprising a priming receptor comprising a first extracellular antigen-binding domain that specifically binds Prostate-Specific Membrane Antigen (PSMA), wherein the priming receptor comprises the sequence as set forth in SEQ ID NO:
- 252 or 127;
- and
- ii. a second chimeric polypeptide comprising a chimeric antigen receptor (CAR) comprising a second extracellular antigen-binding domain that specifically binds to Carbonic Anhydrase IX (CA9), wherein the CAR comprises the sequence as set forth in SEQ ID NO:
- 250 or 108;
- wherein the one or more nucleic acid(s) further comprise a constitutive EF1α promoter comprising the sequence as set forth in SEQ ID NO:
- 179 operably linked to the nucleotide sequence encoding the priming receptor and an inducible promoter comprising the sequence as set forth in SEQ ID NO:
- 256 operably linked to the nucleotide sequence encoding the chimeric antigen receptor.
An ex vivo primary human T cell comprising one or more nucleic acid(s) encoding a system comprising:
- a. a first chimeric polypeptide comprising a priming receptor comprising a first extracellular antigen-binding domain that specifically binds Prostate-Specific Membrane Antigen (PSMA), wherein the priming receptor comprises the sequence as set forth in SEQ ID NO:
- 252 or 127 and
- b. a second chimeric polypeptide comprising a chimeric antigen receptor (CAR) comprising a second extracellular antigen-binding domain that specifically binds to Carbonic Anhydrase IX (CA9), wherein the CAR comprises the sequence as set forth in SEQ ID NO:
- 250 or 108;
- wherein the one or more nucleic acid(s) further comprise a constitutive EF1α promoter comprising the sequence as set forth in SEQ ID NO:
- 179 operably linked to the nucleotide sequence encoding the priming receptor and an inducible promoter comprising the sequence as set forth in SEQ ID NO:
- 256 operably linked to the nucleotide sequence encoding the chimeric antigen receptor.
Dependencies are inferred from the claim text.