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. Author manuscript; available in PMC: 2023 Mar 6.
Published in final edited form as: Mol Cancer Ther. 2022 Sep 6;21(9):1449–1461. doi: 10.1158/1535-7163.MCT-22-0362

Fig. 6.

Fig. 6.

EGCit ADCs exert improved antitumor effects in various xenograft models compared to conventional ADCs. A–D Anti-tumor activity (A, C) and survival benefit (B, D) in orthotopic xenograft mouse models of human breast cancer. KPL-4 model (A, B): a single dose of vehicle control (black circle), Kadcyla® (light purple square), Enhertu® (purple inversed triangle), EVCit-MMAE ADC 4b (green triangle), EGCit-MMAE ADC 4c (magenta square) or EGCit-DuoDM ADC 6 (cyan circle) was intravenously administered at 1 mg kg–1 to tumor-bearing female NSG mice at a mean tumor volume of ~100 mm3 (n = 5 for all groups). JIMT-1/MDA-MB-231 4:1 admixed model (C, D): eight days post implantation (indicated with a black arrow), female NU/J mice were intravenously administered with a single dose of Enhertu® (3 mg kg –1, purple inversed triangle, n = 5) or EGCit-MMAE/F DAR 4+2 dual-drug ADC 7a, (1 mg kg–1, magenta open square, n = 6). Note: The tumor volume and survival curve data of vehicle control (black circle with dotted curve, n = 4) and EVCit dual-drug ADC 7b (1 mg kg–1, green open triangle with dotted curve, n = 5) presented here were previously reported by us(30). Data are presented as mean values ± SEM. E,F study schedule in the U87ΔEGFR-luc orthotopic xenograft model (E) and survival curves after treatment (F). U87ΔEGFR-luc cells were intracranially implanted to male NSG mice. Five days post implantation, mice were intravenously administered with a single dose of vehicle control (black, n = 6), anti-EGFRvIII VCit-MMAE ADC 8a (5 mg kg–1, light purple, n = 6), or anti-EGFRvIII EGCit-MMAE ADC 8b (5 mg kg–1, magenta, n = 7). All animals other than the ones that were found dead or achieved complete remission were killed at the pre-defined humane endpoint, which were counted as deaths. For statistical analysis of the tumor volume data, a Welch’s t-test (two-tailed, unpaired, uneven variance) was used. Kaplan-Meier survival curve statistics were analyzed with a logrank (Mantel–Cox) test. To control the family-wise error rate in multiple comparisons, crude P values were adjusted by the Holm–Bonferroni method. CR, complete remission; DuoDM, duocarmycin DM.