Compositions and methods for targeting CLEC12A-expressing cancers
AssigneeH. Lee Moffitt Cancer Center and Research Institute, Inc.
InventorMarco L. Davila
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Abstract
Disclosed are compositions and methods for targeted treatment of CLEC12A-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill CLEC12A-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a CLEC12A-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs. Also disclosed are multivalent antibodies are disclosed that are able to engage T-cells to destroy CLEC12A-expressing malignant cells.
Claims12
A chimeric antigen receptor (CAR) polypeptide, comprising a CLEC12A antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region,
- wherein the CLEC12A antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CLEC12A,
- wherein the CDR1 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:1;
- the CDR2 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:4 or SEQ ID NO:5;
- the CDR3 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:8;
- the CDR1 sequence of the VL comprises the amino acid sequence SEQ ID NO:10;
- the CDR2 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:13;
- and the CDR3 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:15;
- or
- wherein the CDR1 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:2;
- the CDR2 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:4;
- the CDR3 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:8;
- the CDR1 sequence of the VL comprises the amino acid sequence SEQ ID NO:11;
- the CDR2 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:13;
- and the CDR3 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:15;
- or
- wherein the CDR1 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:3;
- the CDR2 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:4 or SEQ ID NO:5;
- the CDR3 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:9;
- the CDR1 sequence of the VL comprises the amino acid sequence SEQ ID NO:11;
- the CDR2 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:13;
- and the CDR3 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:15.
Dependencies are inferred from the claim text.