Bcma-targeted car-t cell therapy of multiple myeloma

A pharmaceutical composition comprising:

• a) T cells comprising a chimeric antigen receptor (CAR) polypeptide comprising:
• i) an extracellular antigen binding domain comprising a first B-cell maturation antigen (BCMA) binding moiety and a second BCMA binding moiety;
• ii) a transmembrane domain;
• and
• iii) an intracellular signaling domain,
• wherein the first BCMA binding moiety comprises the amino acid sequence of QVKLEESGGGLVQAGRSLRLSCAASEHTF SSHVMGWFRQAPGKERESVAVIGWRDIST S YADSVKGRFTISRDNAKKTLYLQMNSLKPEDTAVYYCAARRIDAADFDSWGQGTQVT VSS (SEQ ID NO:
• 1),
• wherein the second BCMA binding moiety comprises the amino acid sequence of EVQLVESGGGLVQAGGSLRLSCAASGRTFTMGWFRQAPGKEREFVAAISLSPTLAYYAE SVKGRFTISRDNAKNTVVLQMNSLKPEDTALYYCAADRKSVMSIRPDYWGQGTQVTVS S (SEQ ID NO:
• 3);
• and
• b) a pharmaceutically acceptable carrier,
• wherein the pharmaceutical composition comprises 1×106 to 1×108 of the T cells,
• wherein the pharmaceutical composition is formulated for single-dose intravenous administration, and
• wherein the T cells comprising the CAR polypeptide were derived from T cells obtained from a subject with refractory or relapsed multiple myeloma who has received multiple prior lines of therapy comprising a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.