Fig. 4: A single dose of GD2TIF-GLP-1 cells attenuates HFD-induced obesity and diabetes in mice.
From: GD2TIF cells as a platform for single-dose and long-term delivery of biologics
a Schematic representation of constructs used to generate DKO and GD2TIF-GLP-1 cells, DKO: Bcor/Zh3c12a genes double knock out without GD2 CAR expression CD8⁺ T cells; GFP: green fluorescent protein. b Illustration depicting GD2TIF-GLP-1 cells secreting GLP-1. To increase the half-life of GLP-1, the GLP-1 construct used in this study included an IL-2 signal sequence, GLP-1(7-38) with three mutations (A8G, G22E, and R36G), followed by a 3×GGGGS linker and a mouse IgG2a Fc sequence. c Experimental design for the treatment of HFD-induced obesity and diabetes using GD2TIF-GLP-1 cells. Male C57BL/6 mice were fed a HFD for one week before the intravenous transfer of one million DKO or GD2TIF-GLP-1 cells. Body weight, cell kinetics, metabolic phenotyping, Insulin Tolerance Test (ITT), and Glucose Tolerance Test (GTT) were assessed at specified time points. GD2TIF-GLP-1 cell distribution was analyzed at the study endpoint. Age-matched chow-fed mice served as a reference group. HFD: High Fat Diet. d Body weight curves for mice receiving the indicated treatments (n = 6). e Body fat ratio before (week 0) and after (week 8) treatment in the indicated groups (n = 6). f, g ITT results, including glucose levels (f) and relative area under the curve (AUC) (g) for the indicated groups (n = 6). h, i GTT results, including glucose levels (h) and relative AUC (i) for the indicated groups (n = 6). j-m, Metabolic phenotyping of mice following treatment, with 48-hour kinetic measurements post-acclimation (n = 6). j, Respiratory exchange ratio (RER). k, Total energy expenditure. l, Accumulated food intake. m, Physical activity. Data represent the mean ± s.e.m. n indicates the number of mice. Exact P values were determined by two tailed paired Student’s t test (e), one-way ANOVA with Tukey’s multiple comparisons test (g, i), and two-way ANOVA with Bonferroni’s post hoc test (d, f, h, j-m). Source data and exact P values are provided as a Source Data file.
