Fig. 1: Descartes-08 produced from diverse human donors efficiently and selectively kills BCMA+ target cells in vitro and in vivo.
a, Schematic overview of the engineering process used to generate Descartes-08 (DC-08) CAR-T cells. b–d, Flow cytometric analysis of anti-BCMA CAR expression in engineered CD8+ T cells derived from both HDs and individuals with MG. Histograms (b) show surface anti-BCMA CAR expression frequency and MFI. Bar graphs show mean ± s.d. for expression frequency (c) and MFI (d) with all data points shown. Technical replicates were performed in triplicate. e,f, DC-08 mRNA copies per cell (e) and CAR expression (f) on DC-08 from representative HDs were measured via qRT–PCR and flow cytometry, respectively. Triplicate technical replicates were obtained for each sample. g, In vitro cytotoxicity assay using HD-derived DC-08 or unmodified control CD8+ T cells and MM.1S-GFP PC target cells at E:T ratios of 1:2, 1:8 and 1:32. Triplicate technical replicates were obtained for each sample. h,i, Cytotoxicity of DC-08 or unmodified control CD8+ T cells against primary autologous PCs as measured by flow cytometry. DC-08 and controls were derived from healthy (h) or MG (i) donors. Gates show percentages of CD8+ effector and CD27highCD8− PC populations. j–n, Preclinical analysis of DC-08 pharmacokinetics and efficacy in an immunocompromised mouse xenograft model. The study shown is one representative study of more than five analogous experiments with similar results. j, Representative flow cytometry plots of peripheral blood 1 day after T cell infusion (day 8) for analysis of anti-BCMA CAR expression in mice administered unmodified CD8+ T cells or DC-08. k,l, Percentage (k) and MFI (l) of CAR expression on propidium iodide−CD45+CD8+ cells for all mice (n = 5 per group) treated with unmodified CD8+ T cells or DC-08. Bar graphs show mean ± s.e.m. with all data points displayed. m,n, Control of MM.1S-Fluc malignant PC burden in xenograft mouse model after infusion of DC-08 or unmodified CD8+ T cells on day 7. Quantification (m) and images (n) of MM.1S-Fluc bioluminescence (n = 5 per group) are shown. P values were calculated using log-transformed data and two-way repeated-measures ANOVA with Geisser–Greenhouse correction; values in the figure show statistical significance at day 13. Line plot shows mean ± s.e.m. Source data are provided for this figure. rh, recombinant human. Panel a created with BioRender.com.
