Fig. 1: αTIGIT-IL2 exhibits effective tumor control even in the ICB treatment-resistant model. | Nature Communications

Fig. 1: αTIGIT-IL2 exhibits effective tumor control even in the ICB treatment-resistant model.

From: αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models

Fig. 1

a Schematic of immunocytokine generation in this study. b ELISA absorbance measurement of αTIGIT-IL2 and 13G6 binding to plate-bound mouse TIGIT (n = 4 replicates). c The bioactivity of the indicated proteins was detected based on the phosphorylation of STAT5 in the CTLL-2 reporter cell line following exposure for 30 min to increasing concentrations of either rhIL2 or αTIGIT-IL2 (n = 4 replicates). d Blocking efficiency of mouse CD155-TIGIT axis by 13G6 and αTIGIT-IL2. The 293T-mTIGIT cell line was incubated with mCD155-Fc for 1 h following pretreatment with 13G6 or αTIGIT-IL2 for 1 h. The binding of mCD155-Fc with 293T-mTIGIT was detected by flow cytometry (n = 4 replicates). e, m, f 6–8 weeks old female C57BL/6 J mice were subcutaneously inoculated with 2 × 105 MC38 cells. Tumor-bearing mice were intraperitoneally treated with PBS (n = 7 individual animals) or 10 μg αTIGIT-IL2 (n = 8 individual animals) or 20 μg αTIGIT-IL2 (n = 8 individual animals) or 30 μg αTIGIT-IL2 (n = 8 individual animals) on days 7, 10, and 13. Tumor volume (e), body weight (f) were measured as indicated. g Representative hematoxylin and eosin (H&E) staining images of the liver (top) and lung samples (bottom) from C57BL/6 J mice, which were subcutaneously inoculated with 5 × 105 MC38 cells and intraperitoneally treated with PBS or 10 μg αTIGIT-IL or 20 μg αTIGIT-IL2 on day 7 after tumor inoculation. h, i 6–8 weeks old female C57BL/6 J mice (n = 6 individual animals/group) were subcutaneously inoculated with 5 × 105 MC38 cells. Tumor-bearing mice were intraperitoneally treated with PBS or 10 μg αTIGIT-IL2 or αTIGIT-IL2v on days 7, 10, and 13. Tumor volumes (h) were measured as indicated, and growth curves for each individual animal (i) are shown. j, k 6–8 weeks old female C57BL/6 J mice (n = 5 individual animals/group) were subcutaneously inoculated with 5 × 105 MC38 cells. Tumor-bearing mice were intraperitoneally treated with PBS, or 10 μg αTIGIT-IL2, or αPD1-IL2 on days 7, 10, and 13. Tumor volumes (j) were measured as indicated, and growth curves for each individual animal (k) are shown. l, m 6–8 weeks old female C57BL/6 J mice (n = 5 individual animals/group) were subcutaneously inoculated with 5 × 105 MC38 cells. Tumor-bearing mice were intraperitoneally treated with PBS or 10 μg αTIGIT-IL2 or αTIGIT-IL2(LALA-PG) on days 7, 10, and 13. Tumor volumes (l) were measured as indicated, and growth curves for each individual animal (m) are shown. n, o 6–8 weeks old female C57BL/6 J mice (n = 5 individual animals/group) were subcutaneously inoculated with 5 × 105 MC38 cells. Tumor-bearing mice were intraperitoneally treated with PBS, or 15 μg 13G6, or 10 μg αControl-IL2, or 15 μg 13G6 plus 10 μg αControl-IL2, or 10 μg αTIGIT-IL2 on days 7, 10, and 13. Tumor volumes (n) were measured as indicated, and growth curves for each individual animal (o) are shown. p, q 6–8 weeks old female C57BL/6 J mice (n = 6 individual animals/group) were subcutaneously inoculated with 5 × 105 B16F10 cells. Tumor-bearing mice were intraperitoneally injected with PBS, 10 μg αTIGIT-IL2, or αPD1-IL2 on day 4. Tumor volume (q) was measured as indicated. Data represent mean ± SEM from n ≥ 5 independent animals per group. The P-value was determined by 2-way ANOVA with Geisser-Greenhouse correction (e, h, j, l, n, q). Source data are provided as a Source Data file.

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