Improved glycan-dependent immunotherapeutic bi-specific fusion proteins and chimeric antigen receptors
AssigneeThe Regents of the University of California
InventorsMichael DEMETRIOU, Raymond Wenhou ZHOU
Life of this patent
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Abstract
Provided are compositions and methods for treating diseases associated with aberrant glycosylation of cell surface molecules and expression of tumor-associated carbohydrate antigens (TACA). Also provided are bi-specific fusion proteins and chimeric antigen receptors (CARs) specific to tumor-associated carbohydrate antigens (TACA-CARs), vectors encoding the TACA-bi-specific fusion proteins and CARs, and recombinant cells comprising the TACA-bi-specific fusion proteins and CARs.
Claims35
An isolated nucleic acid molecule encoding:
- (i) a bi-specific fusion protein comprising:
- (a) an antigen binding domain that selectively binds a tumor-associated carbohydrate antigen (TACA), and
- (b) an immune cell recognition domain that specifically binds a receptor on an immune effector cell;
- or
- (i) a chimeric antigen receptor (CAR) comprising:
- (a) an antigen binding domain that selectively binds a tumor-associated carbohydrate antigen (TACA):
- (b) a transmembrane domain:
- (c) a costimulatory signaling region;
- and (d) an intracellular signaling domain;
- wherein the antigen binding domain comprises a TACA-binding domain derived from a lectin;
- and wherein the antigen binding domain comprises more than one TACA binding domains.
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A bi-specific fusion protein that selectively binds a tumor-associated carbohydrate antigen (TACA) comprising:
- (i) an antigen binding domain selected from the group consisting of SEQ ID NOs:
- 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 133, 134, 135, 136, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, and 152;
- or an amino acid sequence having at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NOs:
- 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 133, 134, 135, 136, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, or 152;
- and
- (ii) an immune cell recognition domain that specifically binds a receptor on an immune effector cell.
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Dependencies are inferred from the claim text.