Fig. 4: ProCTLA-4 with ADCC enhanced Fc is boosted for anti-tumor efficacy.
From: A next-generation anti-CTLA-4 probody mitigates toxicity and enhances anti-tumor immunity in mice
a MC38-hCTLA-4 cells were incubated with serial dilutions of Ipilimumab (Ipi), ADCC-enhanced Ipilimumab (IpiADCC), ProCTLA-4, or ADCC-enhanced ProCTLA-4 (ProCTLA-4ADCC) for 1 h. Jurkat-LuciaTM NFAT-CD16 effector cells were then co-incubated with MC38-hCTLA-4 cells for 6 h. ADCC response was assessed by Glomax Multi Plus. b MC38 tumor-bearing male hCTLA-4 KI mice were i.p. treated with CTR (n = 9), 40 μg Ipi (n = 10), equimolar IpiADCC (n = 9), ProCTLA-4 (n = 9), or ProCTLA-4ADCC (n = 9) on days 12 and 15. The tumor growth was monitored. c B16F10 tumor-bearing male hCTLA-4 KI mice were i.p. treated with CTR (n = 5), 100 μg Ipi (n = 5), equimolar IpiADCC (n = 4), ProCTLA-4 (n = 5), or ProCTLA-4ADCC (n = 4) on days 12, 15, 18 and 21, and the tumor growth was measured. d–f A549 tumor-bearing humanized male NSG-SGM3 mice engrafted with CD34+ human hematopoietic cells were i.p. treated with CTR (n = 5), 100 μg Ipi (n = 4), equimolar IpiADCC (n = 5), ProCTLA-4 (n = 4), or ProCTLA-4ADCC (n = 5) on days 10, 13, and 16. The tumor growth (d), percentage of body weight change (e), and percentage of survival (f) were monitored. Data in panel (b) are shown as mean ± s.e.m. and are pulled from two independent experiments. Data in panels (c–g) are representative of two independent experiments. Statistical analysis was performed using non-linear best fits (a), two-way ANOVA with Tukey’s multiple comparisons test (b–e) or log-rank (Mantel-Cox) test (f).
