CAR-BCMA T cells specifically recognized BCMA in vitro and exhibited antimyeloma activity in humans. (A) Diagram of the MSGV-11D5-3-CD828Z γ-retroviral vector encoding the anti-BCMA CAR (CAR-BCMA) is shown. CAR-BCMA contained the 11D5-3 anti-BCMA single chain variable fragment (scFv), CD8α hinge and transmembrane regions, the cytoplasmic portion of the CD28 costimulatory moiety, and the CD3ζ T-cell activation domain. (B) CAR-BCMA expression on the surface of the infusion T cells of patient 10 was detected by staining with a PE-BCMA-Fc protein reagent. The plot is gated on live CD3⁺ lymphocytes. (C) Demonstrating specificity, the PE-BCMA-Fc reagent did not stain PBMCs that were not transduced with the CAR-BCMA gene. (D) CAR-BCMA T cells of patient 10 were cultured with target cells that either expressed BCMA (BCMA-K562 and RPMI8226) or did not express BCMA (NGFR-K562 and CCRF-CEM). The CAR-BCMA T cells of patient 10 specifically released IFNγ in response to BCMA-expressing target cells in vitro. (E) Patient 8 who had MM that was progressing despite 8 prior lines of therapy obtained a very good partial remission (VGPR) after infusion of CAR-BCMA T cells. Positron emission tomography–computed tomography scans from before and after treatment show elimination of a large number of MM bone lesions. (F) Patient 8’s free κ light chains level decreased after CAR T-cell infusion as the MM entered a VGPR and then increased with progression of the MM. The serum BCMA protein level followed a pattern similar to that of the serum free κ light chains.