Fig. 6: Tumour-intrinsic CXCL10 expression enhances CAR T cell infiltration in xenograft neuroblastoma models. | Nature Communications

Fig. 6: Tumour-intrinsic CXCL10 expression enhances CAR T cell infiltration in xenograft neuroblastoma models.

From: Personalized CRISPR knock-in cytokine gene therapy to remodel the tumor microenvironment and enhance CAR T cell therapy in solid tumors

Fig. 6: Tumour-intrinsic CXCL10 expression enhances CAR T cell infiltration in xenograft neuroblastoma models.

a Schematic of the xenograft mouse model using immunodeficient NOG (NOD.Cg-Prkdcscid Il2rγtm1Sug/JicTac) mice with subcutaneous transplantation of unmodified SK-N-AS and SK-N-BE2c cells, RPLP0/CHD1 CXCL10 Q8⁺ enriched knock-in cell lines, or a SK-N-BE2c L1CAM knock-out cell line in the left flank. After tumour engraftment, mice were treated with firefly luciferase-expressing L1CAM-targeting CD3⁺ CAR T cells by tail vein injection, followed by repetitive bioluminescence imaging analysis. Representative images of individual animals analysed as groups in (b). Images from all animals are provided in Supplementary Figs. 22 and 23. b Tumoural CAR T cell infiltration over time, represented as the bioluminescence signal in the left flank relative to the tumour size measured on the same day for different treatment groups. The SK-N-AS tumour only group includes four animals that were excluded from CAR T cell treatment due to tumour sizes smaller than 50 mm³ (Supplementary Fig. 24a). c Comparison of total tumoural CAR T cell infiltration and expansion, represented by the area under the curve (AUC) of the bioluminescence-to-tumour volume ratio, and comparison of early infiltration based on the bioluminescence-to-tumour volume ratio on day 4 between treatment groups. d Individual tumour growth curves for all treatment groups. Data presentation: b, c Mean ± SD. Dots in (b) represent mean values and dots in (c) and n represent individual animals. Statistical analysis: (c) Mann-Whitney test (two-sided, exact p = 0.39, 0.026, >0.99, 0.038). p values: *<0.05, **<0.01, ****<0.0001); n.s., not significant. Source data are provided as a Source Data file. Illustration attribution: Elements of tumor cell culture, tumor cell bulk and CAR T cells in (a): Created in BioRender. Kuenkele, A. (2025) https://BioRender.com/u71d212.

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