Effective targeting of primary human leukemia using anti-CD123 chimeric antigen receptor engineered T cells

An isolated nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein said CAR comprises a humanized anti-CD123 binding domain, a transmembrane domain, and an intracellular signaling domain comprising a primary signaling domain, a costimulatory domain, or both a primary signaling domain and a costimulatory domain, and

• wherein said anti-CD123 binding domain comprises:
• (a) a light chain variable region comprising:
• a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO:
• 20, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO:
• 21, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:
• 22, and
• a heavy chain variable region comprising:
• a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO:
• 16, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO:
• 17, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:
• 18;
• or
• (b) a light chain variable region comprising:
• a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO:
• 28, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO:
• 29, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:
• 30, and
• a heavy chain variable region comprising:
• a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO:
• 24, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO:
• 25, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:
• 26;
• or
• (c) a light chain variable region comprising:
• a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO:
• 87, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO:
• 88, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:
• 89, and
• a heavy chain variable region comprising:
• a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO:
• 84, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO:
• 85, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:
• 86.