Systemic low-dose radiation is less debulking than focal high-dose radiation but results in significantly improved response and survival with CAR T cells. (A) Two days after the low-dose (1.8 Gy in 1 fraction) RT or sham procedure, mice were euthanized and the total number of human CD19+ cells were quantified per femur using flow cytometry. (B) Bioluminescence imaging was used to quantify F. Luciferase-expressing tumor cells in vivo over time, after low-dose RT or no treatment. (C) The precise cytotoxic effects of low- vs high- (20 Gy in 4 fractions) dose RT were quantified in vitro over time using flow cytometry, with live cells defined as Zombie NIR negative Annexin-V negative. (D) Bioluminescence imaging of tumor-bearing mice showing systemic tumor distribution (left), and the radiation fields used for focal or systemic tumor targeting (right). (E) Total body tumor burden 1 day after completing systemic (aka total body) low-dose vs focal “debulking” high-dose radiation. Total body tumor burden (F) and overall survival (G) of mice treated with low-dose CAR T cells after the various indicated conditioning regimens. 10 000 CAR T cells were used in these studies.