Figure 2.
GM-CSF neutralization in vivo enhances CAR-T cell antitumor activity in xenograft models. (A) Experimental schema: NSG mice were injected IV with the luciferase+CD19+ cell line NALM6 (1 × 106 cells per mouse). Four to six days later, mice were imaged and randomized, and they received 1 to 1.5 × 106 CART19 cells or an equivalent number of total cells of control UTD cells the following day, with lenzilumab or control IgG (10 mg/kg, given intraperitoneally daily for 10 days, starting on the day of CAR-T injection). Mice were followed with serial bioluminescence imaging to assess disease burden beginning at day 7 post–CAR-T cell injection and were followed for overall survival. Tail vein bleeding was performed 7 or 8 days after CAR-T cell injection. (B) Lenzilumab neutralizes CAR-T–produced serum GM-CSF in vivo compared with isotype-control treatment, as assayed by a GM-CSF singleplex assay; n = 2 experiments, 7 or 8 mice per group, representative experiment, serum from day 8 post–CAR-T cell/UTD cell injection. Data are mean ± SEM. (C) Lenzilumab-treated CAR-T cells and isotype-control–treated CAR-T cells are equally effective at controlling tumor burden in vivo in a high tumor burden relapse xenograft model of ALL, day 7 post–CAR-T injection; n = 2 experiments, 7 or 8 mice per group, a representative experiment is depicted. Data are mean ± SEM. (D) Mouse images from (C). (E) Experimental schema: NSG mice were injected IV with the blasts derived from patients with ALL (1 × 106 cells per mouse). Mice were bled serially and when the CD19+ cells were ∼1 per microliter, mice were randomized to receive 2.5 × 106 CART19 cells with lenzilumab or control IgG (10 mg/kg, given intraperitoneally daily for 10 days, starting on the day of CAR-T injection). Mice were followed with serial tail vein bleeding to assess disease burden beginning at day 14 post–CAR-T cell injection and were followed for overall survival. (F) Lenzilumab treatment with CAR-T therapy results in more sustained control of tumor burden over time in a patient ALL xenograft model compared with isotype-control treatment with CAR-T therapy; 6 mice per group. Data are mean ± SEM. *P < .05, **P < .01, ***P < .001, Student t test. ns, P > .05, Student t test.

GM-CSF neutralization in vivo enhances CAR-T cell antitumor activity in xenograft models. (A) Experimental schema: NSG mice were injected IV with the luciferase+CD19+ cell line NALM6 (1 × 106 cells per mouse). Four to six days later, mice were imaged and randomized, and they received 1 to 1.5 × 106 CART19 cells or an equivalent number of total cells of control UTD cells the following day, with lenzilumab or control IgG (10 mg/kg, given intraperitoneally daily for 10 days, starting on the day of CAR-T injection). Mice were followed with serial bioluminescence imaging to assess disease burden beginning at day 7 post–CAR-T cell injection and were followed for overall survival. Tail vein bleeding was performed 7 or 8 days after CAR-T cell injection. (B) Lenzilumab neutralizes CAR-T–produced serum GM-CSF in vivo compared with isotype-control treatment, as assayed by a GM-CSF singleplex assay; n = 2 experiments, 7 or 8 mice per group, representative experiment, serum from day 8 post–CAR-T cell/UTD cell injection. Data are mean ± SEM. (C) Lenzilumab-treated CAR-T cells and isotype-control–treated CAR-T cells are equally effective at controlling tumor burden in vivo in a high tumor burden relapse xenograft model of ALL, day 7 post–CAR-T injection; n = 2 experiments, 7 or 8 mice per group, a representative experiment is depicted. Data are mean ± SEM. (D) Mouse images from (C). (E) Experimental schema: NSG mice were injected IV with the blasts derived from patients with ALL (1 × 106 cells per mouse). Mice were bled serially and when the CD19+ cells were ∼1 per microliter, mice were randomized to receive 2.5 × 106 CART19 cells with lenzilumab or control IgG (10 mg/kg, given intraperitoneally daily for 10 days, starting on the day of CAR-T injection). Mice were followed with serial tail vein bleeding to assess disease burden beginning at day 14 post–CAR-T cell injection and were followed for overall survival. (F) Lenzilumab treatment with CAR-T therapy results in more sustained control of tumor burden over time in a patient ALL xenograft model compared with isotype-control treatment with CAR-T therapy; 6 mice per group. Data are mean ± SEM. *P < .05, **P < .01, ***P < .001, Student t test. ns, P > .05, Student t test.

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