Disitamab vedotin is an antibody-drug conjugate (ADC) targeting HER2 protein that is comprised of hertuzumab coupling monomethyl auristatin E (MMAE) via a cleavable linker [1]. Disitamab vedotin can kill tumor cells by targeting HER2-protein on the surface of tumor cells, as well as releasing small molecules in lysosomes after endocytosis[2]. Disitamab vedotin has been widely used to inhibit the growth of various drug-resistant cancer cells and tumors in xenograft mouse models[3].
In vitro, Disitamab vedotin treatment for 48 hours significantly inhibited the growth of HT1376 cells, SW780 cells and RT4 cells was, with IC50 values of 158.3μg/ml, 155.7μg/ml and 132.2μg/ml, respectively[4]. Treatment with 50μg/ml Disitamab vedotin for 48 hours impeded the transition from G1 phase to S phase in A549 cells, increased the apoptosis rate and decreased the expression of FOXA1 protein[5]. Treatment with 100μg/ml Disitamab vedotin for 48 hours activated the cGAS-STING pathway in HCT116 cells, inducing cell cycle arrest[6].
In vivo, Disitamab vedotin treatment via weekly intravenous administration of 2.5mg/kg for 3 weeks significantly reduced the tumor volume in the CRC054 xenograft mouse model, without showing any obvious organ toxicity[7]. A single intravenous injection of 5mg/kg of Disitamab vedotin can inhibit tumor growth in the L-JIMT-1 lung metastasis mouse model and reduce vascular volume[8].
References:
[1] Shi F, Liu Y, Zhou X, et al. Disitamab vedotin: a novel antibody-drug conjugates for cancer therapy[J]. Drug Delivery, 2022, 29(1): 1335-1344.
[2] Jiang J, Li S, Shan X, et al. Preclinical safety profile of disitamab vedotin: a novel anti-HER2 antibody conjugated with MMAE[J]. Toxicology letters, 2020, 324: 30-37.
[3] Pourjamal N, Le Joncour V, Vereb G, et al. Disitamab vedotin in preclinical models of HER2-positive breast and gastric cancers resistant to trastuzumab emtansine and trastuzumab deruxtecan[J]. Translational oncology, 2025, 53: 102284.
[4] Li J, Shan K, Huang W, et al. The combination treatment of RC48 and STAT3 inhibitor acts as a promising therapeutic strategy for basal bladder cancer[J]. Frontiers in immunology, 2025, 15: 1432586.
[5] Zhao M, Zhang N, Wang Y, et al. FOXA1, induced by RC48, regulates HER2 transcription to enhance the tumorigenic capacity of lung cancer through PI3K/AKT pathway[J]. Journal of Cancer, 2024, 15(18): 5863.
[6] Wu X, Xu L, Li X, et al. A HER2-targeting antibody-MMAE conjugate RC48 sensitizes immunotherapy in HER2-positive colon cancer by triggering the cGAS-STING pathway[J]. Cell Death & Disease, 2023, 14(8): 550.
[7] Liu H, Zhou D, Liu D, et al. Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer[J]. Cell Death & Disease, 2024, 15(3): 187.
[8] Pourjamal N, Yazdi N, Halme A, et al. Comparison of trastuzumab emtansine, trastuzumab deruxtecan, and disitamab vedotin in a multiresistant HER2-positive breast cancer lung metastasis model[J]. Clinical & Experimental Metastasis, 2024, 41(2): 91-102.
Disitamab vedotin是一种靶向HER2蛋白的抗体药物偶联物，由hertuzumab通过可裂解连接子与monomethyl auristatin E (MMAE)偶联而成[1]。Disitamab vedotin既可通过靶向肿瘤细胞表面的HER2蛋白杀伤肿瘤细胞，也可在内吞后于溶酶体中释放小分子发挥作用[2]。Disitamab vedotin已被广泛用于抑制异种移植小鼠模型中多种耐药癌细胞和肿瘤的生长[3]。
在体外，Disitamab vedotin处理48小时显著抑制了HT1376细胞、SW780细胞和RT4细胞的生长，IC50值分别为158.3μg/ml、155.7μg/ml和132.2μg/ml [4]。用50μg/ml的Disitamab vedotin处理A549细胞48小时，阻碍了细胞从G1期向S期的转变，增加了凋亡率并降低了FOXA1蛋白的表达[5]。用100μg/ml的Disitamab vedotin处理HCT116细胞48小时，激活了cGAS-STING通路，诱导了细胞周期阻滞[6]。
在体内，每周静脉注射2.5mg/kg剂量的Disitamab vedotin，连续3周，显著减少了CRC054异种移植小鼠模型中的肿瘤体积，且未表现出明显的器官毒性[7]。单次静脉注射5mg/kg剂量的Disitamab vedotin，可抑制L-JIMT-1肺转移小鼠模型中的肿瘤生长并减少血管体积[8]。