PMC9150173_01
Schematic illustration of the CAR construct and treatment timeline. (A) Composition of CAR molecule. (B) Clinical study design.
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The schematic structure of BCMA CAR construct is shown in  Figure 1A , using a murine scFv against BCMA, CD8alpha hinge and transmembrane region, 4-1BB co-stimulatory domain, together with CD3zeta signaling domain. About 30% of CAR-T cells were central memory T cells (CD45RA-CD62L+), 65% were naive and stem cell memory T cells (CD45RA+CD62L+), 2.3% were effector memory T cells (CD45RA-CD62L-), and 2.7% were effector T cells (CD45RA+CD62L-) based on flow cytometry analysis shown in  Supplementary Figure S1 . A schematic design of the clinical trial is shown in  Figure 1B .
Evaluation of CAR ratio, the number of CAR-T cells and cytokines in the peripheral blood. (A) The ratio of BCMA CAR-T cells in total lymphocytes (CAR%) and the absolute number of BCMA CAR-T cells (CAR#) in the peripheral blood of the patient were detected using flow cytometry at the indicated days after CAR-T infusion. (B) The expression levels of cytokines (IL-6, IL-10, and IFN-gamma) in the peripheral blood were evaluated using cytometric bead array after CAR-T infusion at the indicated time points.
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CAR-T ratio, CAR-T cell number, and cytokine levels. CAR-T cells expanded and reached the maximal level in peripheral blood on day 7 post-infusion ( Figure 2A ). IL-6 was highest on day 14 (87.4 pg/mL,  Figure 2B ). In accordance with the cytokine expression, the patient experienced grade 1 CRS and developed symptoms of fever (Tmax, 39.2 C) and headache on day 7.
The concentrations of IgA and M spike before and after BCMA CAR-T cell infusion.
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The level of M-spike remained negative even at 3 months ( Figure 3 ).
Improvement of abnormal signals in right parietal lobe region (sagittal plane and transverse plane) before and after CAR-T infusion.
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CNS-involved tumors were eradicated. Cranial and orbital MRI showed no abnormalities, and previous abnormal signals in the right parietal lobe region disappeared ( Figure 4 ).