Chimeric antigen receptors targeting tim-1
AssigneesCeldara Medical, LLC, Celldex Therapeutics, Inc.
InventorsTerrance A. STADHEIM, Joana M. MURAD, Jake REDER, Henry C. MARSH, JR., Li-Zhen HE, Tibor KELER
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Abstract
The invention provides chimeric antigen receptors (CARs) that specifically bind to the T-cell immunoglobulin and mucin domain 1 (TIM-1) protein. The invention further relates to modified immune cells, e.g., T or NK cells, comprising such CARs, CAR-encoding nucleic acids, CAR-encoding vectors, and methods of making such compositions. The invention further relates to methods for therapeutic use of these CARs and modified immune cells for the treatment of a condition, disorder, or disease associated with cells expressing TIM-1 (e.g., cancer).
Claims50
An isolated chimeric antigen receptor (CAR) comprising (i) an antigen-binding domain that binds to TIM-1;
- (ii) a transmembrane domain;
- and (iii) at least one intracellular signaling domain.
An isolated CAR comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of
- (i) 272H-BB (SEQ ID NO:
- 222);
- (ii) 272H-CD28 (SEQ ID NO:
- 223);
- (iii) 272H-DAP10 (SEQ ID NO:
- 224);
- (iv) 2592H-BB (SEQ ID NO:
- 226);
- (v) 2592H-CD28 (SEQ ID NO:
- 227);
- (vi) 2592H-DAP10 (SEQ ID NO:
- 228);
- or
- (vii) 2592L-CD28 (SEQ ID NO:
- 229);
- or having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%0, or 100% identity to the amino acid sequence encoded by SEQ ID NO:
- 272, 273, 274, 276, 277, 278, 279.
The recombinant or isolated cell according to any one of claims 30-33, which is a T cell or a T cell progenitor cell.
A method for stimulating an immune cell-mediated response in a subject, the method comprising administering to a subject in need thereof an effective amount of an immune cell modified to express a CAR comprising (i) an antigen-binding domain that binds to TIM-1;
- (ii) a transmembrane domain;
- and (iii) at least one intracellular signaling domain, wherein the modified immune cell is activated or stimulated to proliferate when the CAR binds to TIM-1 thereby stimulating an immune cell-mediated response in the subject.
A method for treating a disease, a disorder, or a condition associated with undesired proliferation of cells expressing TIM-1 in a subject, the method comprising administering to the subject in need thereof an effective amount of an immune cell genetically modified to express a CAR comprising (i) an antigen-binding domain that binds to TIM-1;
- (ii) a transmembrane domain;
- and (iii) at least one intracellular signaling domain, wherein the modified immune cell is activated or stimulated to proliferate when the CAR binds to TIM-1 thereby treating the disease, disorder, or condition associated with undesired proliferation of cells expressing TIM-1.
A method for treating a cancer in a subject, the method comprising administering to the subject in need thereof an effective amount of an immune cell modified to express a CAR comprising (i) an antigen-binding domain that binds to TIM-1, (ii) a transmembrane domain, and (iii) at least one intracellular signaling domain.
Dependencies are inferred from the claim text.