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. Author manuscript; available in PMC: 2021 Nov 5.
Published in final edited form as: Nat Cancer. 2021 Sep 23;2(9):904–918. doi: 10.1038/s43018-021-00244-2

Figure 1. Single or dual antigen targeting and single or dual CD28 or 4-1BB costimulation do not eradicate the tumor in stress conditions.

Figure 1.

(a) Schema of the CHLA-255 metastatic xenograft NB model in NSG mice inoculated via tail injection with FFLuc-labelled CHLA-255 cells and treated 14 days later with low doses of CAR-T cells targeting either GD2 (GD2.28ζ and GD2.BBζ) or B7-H3 (B7-H3.28ζ and B7-H3.BBζ) or control CD19.28ζ. (b,c) Representative tumor bioluminescence (BLI) images (b) and BLI kinetics (c) of FFLuc-CHLA-255 tumor growth in the metastatic xenograft NB model shown in (a) (n = 5 mice/group). (d) Kaplan-Meier survival curve of mice in (b, c) (n = 5 mice/group); Comparison of survival curves were determined by Log-rank test, **p = 0.0027 for CD19.28ζ vs. all other groups, **p = 0.0027 for GD2.28ζ vs. B7-H3.BBζ, GD2.BBζ vs. B7-H3.BBζ, and B7-H3.28ζ vs. B7-H3.BBζ, **p = 0.0018 for GD2.28ζ vs. GD2.BBζ, and GD2.28ζ vs. B7-H3.28ζ, **p = 0.0018 for GD2.BBζ vs. B7-H3.28ζ. (e) Schema of the CHLA-255 metastatic xenograft NB model in NSG mice inoculated via tail vein injection with FFLuc-labelled CHLA-255 cells and treated 14 days later with low doses of GD2.28ζ, GD2.28.BBζ, GD2.28ζ/B7-H3.BBζ, and control CD19.28ζ CAR-T cells. (f,g) Representative tumor BLI (f) and BLI kinetics (g) of FFLuc-CHLA-255 tumor growth in the metastatic xenograft NB models shown in (e) (n = 4 or 5 mice/group). (h) Kaplan-Meier survival curve of mice in (f,g) (n = 4 or 5 mice/group); Comparison of survival curves were determined by Log-rank test, **p = 0.0072 for CD19.28ζ vs. GD2.28ζ, **p = 0.0027 for CD19.28ζ vs. GD2.28.BBζ and CD19.28ζ vs. GD2.28ζ/B7-H3.BBζ, *p = 0.0350 for GD2.28ζ vs. GD2.28ζ/B7-H3.BBζ, *p = 0.0157 for GD2.28.BBζ vs. GD2.28ζ/B7-H3.BBζ.