Disrupting tumor tissues by targeting fibroblast activation protein (FAP)
AssigneeThe Trustees of the University of Pennsylvania
InventorsSteven A. Albelda, Ellen Puré, Leslie Todd
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Abstract
The present invention relates to compositions and methods comprising a chimeric antigen receptor (CAR) capable of binding fibroblast activation protein (FAP) for use in treating diseases, disorders or conditions associated with the expression of FAP on canine, mouse, or human tumor-associated cells.
Claims12
A nucleic acid comprising a polynucleotide sequence encoding a chimeric antigen receptor (CAR) capable of binding FAP, comprising an antigen-binding domain, a transmembrane domain, and an intracellular domain, wherein the antigen-binding domain comprises:
- a heavy chain variable region that comprises three heavy chain complementarity determining regions (HCDRs), wherein HCDR1 comprises the amino acid sequence YTITSYSLH (SEQ ID NO:
- 1), HCDR2 comprises the amino acid sequence EINPANGDHNFSEKFEIK (SEQ ID NO:
- 2), and HCDR3 comprises the amino acid sequence LDDSRFHWYFDV (SEQ ID NO:
- 3);
- and
- a light chain variable region that comprises three light chain complementarity determining regions (LCDRs), wherein LCDR1 comprises the amino acid sequence TASSSVSYMY (SEQ ID NO:
- 4), LCDR2 comprises the amino acid sequence LTSNLA (SEQ ID NO:
- 5), and LCDR3 comprises the amino acid sequence QQWSGYPPIT (SEQ ID NO:
- 6).
A nucleic acid comprising a polynucleotide sequence at least 80% identical to the sequence selected from the group consisting of SEQ ID NO:
- 22 and 24.
A modified cell comprising a chimeric antigen receptor (CAR) capable of binding fibroblast activation protein (FAP), wherein the modified cell is selected from the group consisting of an immune cell and a precursor cell thereof, and wherein the CAR comprises:
- a heavy chain variable region that comprises three heavy chain complementarity determining regions (HCDRs), wherein HCDR1 comprises the amino acid sequence YTITSYSLH (SEQ ID NO:
- 1), HCDR2 comprises the amino acid sequence EINPANGDHNFSEKFEIK (SEQ ID NO:
- 2), and HCDR3 comprises the amino acid sequence LDDSRFHWYFDV (SEQ ID NO:
- 3);
- and
- a light chain variable region that comprises three light chain complementarity determining regions (LCDRs), wherein LCDR1 comprises the amino acid sequence TASSSVSYMY (SEQ ID NO:
- 4), a LCDR2 comprises the amino acid sequence LTSNLA (SEQ ID NO:
- 5), and LCDR3 comprises the amino acid sequence QQWSGYPPIT (SEQ ID NO:
- 6).
Dependencies are inferred from the claim text.