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To evaluate the antitumor activity of the novel antibody-drug conjugate (ADC) hIMB1636-MMAE against human epidermal carcinoma, this study systematically investigated its therapeutic efficacy and mechanism of action in A431 cells. Trophoblast cell surface antigen 2 (TROP2) expression in A431 cells was confirmed by Western blot. Flow cytometry was used to analyze the binding characteristics of hIMB1636-MMAE to A431 cells and its effects on cell cycle arrest and apoptosis. The internalization process of the ADC was visualized using confocal laser scanning microscopy, while cytotoxicity in vitro was assessed via the CCK-8 assay. Moreover, an A431 cell-derived xenograft model was established in nude mice to evaluate the in vivo antitumor efficacy of hIMB1636-MMAE. Results showed that A431 cells exhibited high TROP2 expression. hIMB1636-MMAE could specifically bind to A431 cells, and was effectively internalized and transported to lysosomes. Furthermore, hIMB1636-MMAE specifically killed cancer cells with IC50 value of 1.49 ± 0.22 nmol·L-1, and induced G2/M phase cell cycle arrest and apoptosis. In A431 cell-derived xenografts, hIMB1636-MMAE at 10 mg·kg-1 exhibited a significant antitumor effect, achieving a tumor inhibition rate of 93.89% (all animal protocols were approved by the Animal Care and Use Committee at the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, No. IMB-20220210D203). In conclusion, hIMB1636-MMAE demonstrates promising potential against skin cancer and may serve as a candidate therapeutic for TROP2-positive cutaneous malignancies.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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