Cancer immunotherapy using cd19-directed chimeric antigen receptors

A method of treating a cancer using immunotherapy, the method comprising:

• administering to a subject having the cancer a population of immune cells that express a CD19-directed chimeric antigen receptor, the chimeric antigen receptor comprising:
• an extracellular anti-CD19 binding moiety,
• wherein the anti-CD19 binding moiety comprises a heavy chain variable (VH) domain and a and a light chain variable (VL) domain,
• the VH domain comprising a VH domain resulting from humanization of the VH domain amino acid sequence set forth in SEQ ID NO:
• 33,
• the VL domain resulting from humanization of the VL domain amino acid sequence set forth in SEQ ID NO:
• 32.
• a hinge and/or transmembrane domain,
• an intracellular signaling domain,
• wherein the intracellular signaling domain comprises an OX40 subdomain, and
• wherein the cell also expresses membrane-bound interleukin-15 (mbIL15).

A method of treating a cancer using immunotherapy, the method comprising:

• administering to a subject having the cancer a population of immune cells that express a CD19-directed chimeric antigen receptor, the chimeric antigen receptor comprising:
• an extracellular anti-CD19 binding moiety comprising a variable heavy (VH) domain and a variable light (VL) domain;
• and
• an intracellular signaling domain, wherein the intracellular signaling domain comprises:
• an OX40 subdomain and a CD3 zeta subdomain;
• and
• wherein the polynucleotide also encodes membrane-bound interleukin-15 (mbIL15).