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. Author manuscript; available in PMC: 2024 Nov 25.
Published in final edited form as: Nat Biomed Eng. 2023 Nov 30;8(4):380–396. doi: 10.1038/s41551-023-01143-w

Figure 5: Leucine zipper ectodomains enable the generation of ZipRs from diverse cytokine receptor families.

Figure 5:

(a-c) Transduction efficiency (left) and pSTAT3 (a,b) or pSTAT4 (c) expression (right) in Zip21R (a), Zip10R or Zip22R (b), or Zip12R (c) T cells (mean±SD, **p<0.01, ***p<0.001, paired t-test (a,c), one-way ANOVA (b)). (d) Transduction efficiency of B7-H3 CAR and Zip21R in human T cells as measured by flow cytometry for ZipR (mClover) and CAR (anti-human F(ab’)2) (N=4, mean±SD). (e) Fold expansion of CAR or CAR.Zip21R T cells in repeat stimulation assay with A549 WT cells (N=5). (f) Stimulations of tumor cell killing by CAR- or CAR.Zip21R-expressing cells in repeat stimulation assay with A549 WT cells (mean±SD, *p<0.05, paired t-test). (g) Transduction efficiency of B7-H3-CAR and Zip12R in human T cells as measured by flow analysis for the ZipR (mClover) and CAR (anti-human F(ab’)2) (N=3, mean±SD). (h) Fold expansion of CAR or CAR.Zip12R T cells in repeat stimulation assay with A549 WT cells (N=3). (i) Stimulations of tumor cell killing by CAR- or CAR.Zip21R-expressing cells in repeat stimulation assay with A549 WT cells (N=3). (j) Experimental scheme of i.v. A549.GFP.ffLuc model; mice received a single i.v. dose of 3×105 CAR T cells on day 7 post tumor cell injection. (k) Tumor burden in the lungs of treated mice as determined by serial bioluminescence imaging (N=4-5). (l) Kaplan-Meier survival curve (N=4-5, *p<0.05, log rank test). (m) Tumor burden in the lungs of treated mice as determined by serial bioluminescence imaging (N=5). (n) Kaplan-Meier survival curve (N=5, **p<0.001, log rank test).