Fig. 4: T1 and T3 cells deplete patient-derived cancer cells while sparing normal B and T lymphocytes and nonlineage-committed hematopoietic progenitor cells.

a, Representative t-SNE plots showing live HLA-A2^pos, TdT^pos B-ALL tumor cells (CD19⁺CD10⁺ events, left) and T-ALL tumor cells (CD5⁺CD7⁺CD99⁺ and surface CD3⁻CD4⁻ events, right), normal B cells (CD19⁺CD10⁻), normal T cells (CD3⁺ and CD8⁺ or CD4⁺) and CD34⁺lin⁻ progenitor cells following 72 h of coculture with mock-, T1- or T3-transduced T cells (E/T ratio, 1/1), as quantified by flow cytometry. b, Diagnostic samples from 12 patients (Pt.) with HLA-A2^pos, TdT^pos B-ALL or T-ALL, assayed as described in a. Each dot represents the number of live tumor, normal B or T cells after coculture with T1 (green) or T3 (purple) cells, as percentage of corresponding numbers in cultures treated with mock-transduced T cells (gray). c, Dots showing numbers of live CD34⁺lin⁻ cells after coculture with T1 (green) and T3 (purple) cells as percentage of corresponding numbers in cocultures treated with mock-transduced T cells (gray). b,c, Data points represent three or four technical replicates and horizontal lines denote mean. Data shown are from one experiment representative of at least two performed for each patient sample. d, t-SNE plot of PB diagnostic sample from B-ALL patient no. 1N after 72 h of coculture with autologous T cells transduced with T1, T3 or mock. a,d, Inset numbers denote absolute event counts of the indicated cell populations. e, Tandem mass spectrometry fragmentation spectra of TdT peptide-1 and -3 identified from leukemia cells of patient no. 119N. f, Expression of CD19 and TdT in leukemia cells before and after relapse from CD19-specific CAR T-cell therapy in two patients with B-ALL. Ctrl, control. g, Expression of TdT in leukemia cells from a patient with T-ALL at the time of primary diagnosis (Dx) and at relapse after chemotherapy.

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