Chimeric receptors and methods of use thereof

A chimeric protein comprising an antigen-binding domain specific for endomucin (EMCN) and a heterologous molecule or moiety,

• wherein the antigen-binding domain comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein
• (a) the VH comprises:
• a heavy chain complementarity determining region 1 (CDR-H1) having the amino acid sequence of RYDMH (SEQ ID NO:
• 102),
• a heavy chain complementarity determining region 2 (CDR-H2) having the amino acid sequence of VIWGNGNTHYHSALKS (SEQ ID NO:
• 103), and
• a heavy chain complementarity determining region 3 (CDR-H3) having the amino acid sequence of RIKD (SEQ ID NO:
• 4), and
• the VL comprises:
• a light chain complementarity determining region 1 (CDR-L1) having the amino acid sequence of KSSQSLVASDENTYLN (SEQ ID NO:
• 10),
• a light chain complementarity determining region 2 (CDR-L2) having the amino acid sequence of QVSKLDS (SEQ ID NO:
• 11), and
• a light chain complementarity determining region 3 (CDR-L3) having the amino acid sequence of LQGIHLPWT (SEQ ID NO:
• 12), and
• wherein the amino acid sequences of the CDR-H1, the CDR-H2, the CDR-H3, the CDR-L1, the CDR-L2, and the CDR-L3 of the reference antibody are defined based on the Kabat numbering scheme;
• or
• (b) the VH comprises:
• a heavy chain complementarity determining region 1 (CDR-H1) having the amino acid sequence of GFSLSRY (SEQ ID NO:
• 2), a heavy chain complementarity determining region 2 (CDR-H2) having the amino acid sequence of WGNGN (SEQ ID NO:
• 3), and a heavy chain complementarity determining region 3 (CDR-H3) having the amino acid sequence of RIKD (SEQ ID NO:
• 4), and
• the VL comprises:
• a light chain complementarity determining region 1 (CDR-L1) having the amino acid sequence of KSSQSLVASDENTYLN (SEQ ID NO:
• 10), a light chain complementarity determining region 2 (CDR-L2) having the amino acid sequence of QVSKLDS (SEQ ID NO:
• 11), and a light chain complementarity determining region 3 (CDR-L3) having the amino acid sequence of LQGIHLPWT (SEQ ID NO:
• 12), and
• wherein the amino acid sequences of the CDR-H1, the CDR-H2, the CDR-H3, the CDR-L1, the CDR-L2, and the CDR-L3 of the reference antibody are defined based on the Chothia numbering scheme;
• or
• (c) the VH comprises:
• a heavy chain complementarity determining region 1 (CDR-H1) contained within the VH region amino acid sequence of SEQ ID NO:
• 1, a heavy chain complementarity determining region 2 (CDR-H2) contained within the VH region amino acid sequence of SEQ ID NO:
• 1, and a heavy chain complementarity determining region 3 (CDR-H3) contained within the VH region amino acid sequence of SEQ ID NO:
• 1, and
• the VL comprises:
• a light chain complementarity determining region 1 (CDR-L1) are contained within the VL region amino acid sequence of SEQ ID NO:
• 9, a light chain complementarity determining region 2 (CDR-L2) are contained within the VL region amino acid sequence of SEQ ID NO:
• 9, and a light chain complementarity determining region 3 (CDR-L3) are contained within the VL region amino acid sequence of SEQ ID NO:
• 9, and
• optionally wherein the amino acid sequences of the CDR-H1, the CDR-H2, the CDR-H3, the CDR-L1, the CDR-L2, and the CDR-L3 of the reference antibody are defined based on the Kabat or Chothia numbering scheme.