Fig. 4: CD19 negative relapse with preserved CD22 site density after CD19-22.BB.z-CAR and diminished CAR T functionality against CD22. | Nature Medicine

Fig. 4: CD19 negative relapse with preserved CD22 site density after CD19-22.BB.z-CAR and diminished CAR T functionality against CD22.

From: CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial

Fig. 4

a, Antigen density of patient S24 demonstrating both CD19 and CD22 expression preCD19-22.BB.z (top) with loss of CD19 and preservation of CD22 at progression (bottom, green arrows). b, CD19 and CD22 assessment by conventional flow cytometry in patients with B-ALL pretreatment and postprogression demonstrates CD19 loss with CD22 preservation. c, In B-ALL, 3 of 4 patients with antigen quantification pre- and postCD19-22-CD.BB.z demonstrated loss of CD19 expression associated with preserved CD22 expression. d, CD19 and CD22 antigen density at progression (n = 11 patients) after CD19-22.BB.z, with patient S24 highlighted in green. Six patients had <1,150 CD19 molecules per cell with a median CD22 of approximately 6,000 molecules per cell. Dashed line denotes the cutoff at 3,000 CD19 molecules per cell. e, Schematic of CD19-22.BB.z bispecific CAR, displaying the loop structure. f, Histogram of CD19 and CD22 expression on NALM6 lines tested in g–j. g, ICS heatmap representing the secretion or expression of CD69, CD107a, TNF-α, IFN-γ and IL-2 from CD19-22.BB.z infusion products (n = 11 individual products) stimulated with the NALM6 tumors lines from f. The heatmap shows greater activation and secretion of cytokines with stimulation with N6-CD19 and N6-CD19/22 lines versus N6-CD22 stimulation. h, Schematic of bispecific CD19-22.BB.z versus monospecific CD22.BB.z. i, ICS stimulation of CD19-22.BB.z (n = 11) versus monospecific CD22.BB.z (n = 5) CAR products against the CD22high cell line shows increased cytokine secretion of IL-2 and TNF-α through the monospecific CAR22.BB.z (two-tailed t-test). j, Using the single-cell IsoPlexis platform, stimulation of clinical products (n = 7 individual products) with N6-CD19 showed a higher PSI compared to N6-CD22. The CD22 scFV on the bispecific CAR had lower PSI compared to the monospecific CAR22.BB.z (n = 4 individual products) when stimulated with N6-CD22 (Mann–Whitney U-test).

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