Figure 6
Figure 6. Effects of CY lymphodepletion and IL-2 on lymphocyte subsets and cytokine levels. Multiparameter flow cytometry was performed with patient peripheral blood samples collected at baseline and at serial time points after T-cell infusions to quantify (A) all lymphocytes and CD4+ and CD8+ T cells, expressed as percentage change from baseline and (B) absolute numbers of Treg cells (CD4+/FoxP3+) and the ratios of Treg to CD4+ T cells and CD8+ T cells for UPN-02 (●), UPN-03 (■), and UPN-04 (▴). (C) CD19+ and CD20+ B cells, expressed as percentage change from baseline. (D) Levels of multiple cytokines were measured in patient serum samples collected at serial time points after CY administration using a Luminex microbead immunoassay and expressed as fold change from baseline (day −15, day −9, and day 0 before CY for UPN-02, UPN-03, and UPN-04, respectively). The range and baseline values (listed in parentheses sequentially for patients UPN-02, UPN-03, and UPN-04) in picograms per milliliter are as follows: IL-2: < 8 to 413 (90.9, 32.7, < 8); IL-4: < 2 to 298 (50.2, 10.6, < 2); IL-6: < 2 to 174 (58.0, 11.7, 2.73); IL-7: 4.53 to 336 (49.7, 14.9, 6.41); IL-10: < 1 to 526 (41.3, 29.4, < 1); IL-12p70: < 8 to 2011 (328, 16.3, < 8); IL-15: 1.61 to 76.4 (21.5, 4.69, 1.74); IL-17: < 15 to 412 (27.3, < 15, < 15); IL-21: < 15 to 4997 (685, 151, < 15); IFN-γ: 1.6 to 23.1 (8.18, 2.52, 1.70); TNF-α: < 3.6 to 164 (28.6, 8.58, < 3.6); and MIP1-α: < 300 to 868 (335, < 300, < 300). Arrows indicate infusions of genetically modified T cells; and black bar, the 14-day period of low-dose IL-2 injections.

Effects of CY lymphodepletion and IL-2 on lymphocyte subsets and cytokine levels. Multiparameter flow cytometry was performed with patient peripheral blood samples collected at baseline and at serial time points after T-cell infusions to quantify (A) all lymphocytes and CD4+ and CD8+ T cells, expressed as percentage change from baseline and (B) absolute numbers of Treg cells (CD4+/FoxP3+) and the ratios of Treg to CD4+ T cells and CD8+ T cells for UPN-02 (●), UPN-03 (■), and UPN-04 (▴). (C) CD19+ and CD20+ B cells, expressed as percentage change from baseline. (D) Levels of multiple cytokines were measured in patient serum samples collected at serial time points after CY administration using a Luminex microbead immunoassay and expressed as fold change from baseline (day −15, day −9, and day 0 before CY for UPN-02, UPN-03, and UPN-04, respectively). The range and baseline values (listed in parentheses sequentially for patients UPN-02, UPN-03, and UPN-04) in picograms per milliliter are as follows: IL-2: < 8 to 413 (90.9, 32.7, < 8); IL-4: < 2 to 298 (50.2, 10.6, < 2); IL-6: < 2 to 174 (58.0, 11.7, 2.73); IL-7: 4.53 to 336 (49.7, 14.9, 6.41); IL-10: < 1 to 526 (41.3, 29.4, < 1); IL-12p70: < 8 to 2011 (328, 16.3, < 8); IL-15: 1.61 to 76.4 (21.5, 4.69, 1.74); IL-17: < 15 to 412 (27.3, < 15, < 15); IL-21: < 15 to 4997 (685, 151, < 15); IFN-γ: 1.6 to 23.1 (8.18, 2.52, 1.70); TNF-α: < 3.6 to 164 (28.6, 8.58, < 3.6); and MIP1-α: < 300 to 868 (335, < 300, < 300). Arrows indicate infusions of genetically modified T cells; and black bar, the 14-day period of low-dose IL-2 injections.

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