Figure 7.

NKTR-255 increases human CAR T-cell accumulation and survival in the bone marrow of lymphoma-bearing mice. NSG mice were injected IV with 5 × 10⁵ Raji cells. Seven days later, tumor-bearing mice received 0.8 × 10⁶ CD19 CAR T cells (1:1, CD8⁺:CD4⁺) IV. Cohorts of mice (n = 3 per group) received either buffer or NKTR-255 at 0.3 mg/kg IV weekly starting on day 7 and euthanized on days 8, 11, 14, 21, and 28. Mice euthanized on days 14, 21, and 28 did not receive second, third, and fourth dose of NKTR-255, respectively. Single-cell suspensions from the bone marrow were analyzed by flow cytometry. (A) Percentage of Ki-67⁺ CD8⁺ (left) and CD4⁺ (right) CAR T cells in the bone marrow at the indicated time points. (B) BCL-2 expression (MFI) in CD8⁺ (left) and CD4⁺ (right) CAR T cells at indicated time points. (C) Absolute numbers of CD8⁺ (left) and CD4⁺ (right) CAR T cells at the indicated time points. (D) AUC_0-28 of CD8⁺ and CD4⁺ CAR T-cell counts in the bone marrow. The figures show the mean ± SEM. An unpaired t test with a false discovery rate of 1% using the 2-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli were used to compare differences between groups.