Treatment of cancer using a CD123 chimeric antigen receptor

A method of treating a mammal having a disease associated with a cell which expresses CD123, comprising administering to the mammal an effective amount of an immune effector cell comprising:

• (a) an isolated nucleic acid molecule encoding a CAR, wherein the CAR comprises a CD123 binding domain, a transmembrane domain, and an intracellular signaling domain, and wherein the encoded CD123 binding domain comprises:
• (i) a heavy chain variable domain comprising three complementary determining regions of heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) present in order of HC CDR1, HC CDR2, and HC CDR3, wherein HC CDR1 comprises the amino acid sequence of SEQ ID NO:
• 487, HC CDR2 comprises the amino acid sequence of SEQ ID NO:
• 492, and HC CDR3 comprises the amino acid sequence of SEQ ID NO:
• 497;
• and
• a light chain variable domain comprising three complementary determining regions of light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) present in order of LC CDR1, LC CDR2, and LC CDR3, wherein LC CDR1 comprises the amino acid sequence of SEQ ID NO:
• 502, LC CDR2 comprises the amino acid sequence of SEQ ID NO:
• 507, and LC CDR3 comprises the amino acid sequence of SEQ ID NO:
• 512;
• or
• (ii) a heavy chain variable domain comprising three complementary determining regions of heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) present in order of HC CDR1, HC CDR2, and HC CDR3, wherein HC CDR1 comprises the amino acid sequence of SEQ ID NO:
• 517, HC CDR2 comprises the amino acid sequence of SEQ ID NO:
• 522, and HC CDR3 comprises the amino acid sequence of SEQ ID NO:
• 527;
• and
• a light chain variable domain comprising three complementary determining regions of light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) present in order of LC CDR1, LC CDR2, and LC CDR3, wherein LC CDR1 comprises the amino acid sequence of SEQ ID NO:
• 532, LC CDR2 comprises the amino acid sequence of SEQ ID NO:
• 537, and LC CDR3 comprises the amino acid sequence of SEQ ID NO:
• 542;
• or
• (iii) a heavy chain variable domain comprising three complementary determining regions of heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) present in order of HC CDR1, HC CDR2, and HC CDR3, wherein HC CDR1 comprises the amino acid sequence of SEQ ID NO:
• 335, HC CDR2 comprises the amino acid sequence of SEQ ID NO:
• 363, and HC CDR3 comprises the amino acid sequence of SEQ ID NO:
• 391;
• and
• a light chain variable domain comprising three complementary determining regions of light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) present in order of LC CDR1, LC CDR2, and LC CDR3, wherein LC CDR1 comprises the amino acid sequence of SEQ ID NO:
• 419, LC CDR2 comprises the amino acid sequence of SEQ ID NO:
• 447, and LC CDR3 comprises the amino acid sequence of SEQ ID NO:
• 475, or
• (b) an isolated CAR polypeptide molecule encoded by the nucleic acid molecule of (a).