Georgetown University Medical Center, Washington, DC, USA.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Br J Cancer. 2022 Mar;126(5):754-763. doi: 10.1038/s41416-021-01658-6. Epub 2021 Dec 7.
Thymic epithelial tumours (TETs) are rare tumours comprised of thymomas and thymic carcinoma. Novel therapies are needed, especially in thymic carcinoma where the 5-year survival rate hovers at 30%. Mesothelin (MSLN), a surface glycoprotein that is cleaved to produce mature MSLN (mMSLN) and megakaryocyte potentiating factor (MPF), is expressed in limited tissues. However, its expression is present in various cancers, including thymic carcinoma, where it is expressed in 79% of cases.
We utilised flow cytometry, in vitro cytotoxicity assays, and an in vivo xenograft model in order to demonstrate the ability of the MSLN targeting antibody-drug conjugate (ADC) anetumab ravtansine (ARav) in inhibiting the growth of thymic carcinoma.
Thymoma and thymic carcinoma cell lines express MSLN, and anetumab, the antibody moiety of ARav, was capable of binding MSLN expressing thymic carcinoma cells and internalising. ARav was effective at inhibiting the growth of thymic carcinoma cells stably transfected with mMSLN in vitro. In vivo, 15 mg/kg ARav inhibited T1889 xenograft tumour growth, while combining 7.5 mg/kg ARav with 4 mg/kg cisplatin yielded an additive effect on inhibiting tumour growth.
These data demonstrate that anetumab ravtansine inhibits the growth of MSLN positive thymic carcinoma cells in vitro and in vivo.
胸腺瘤上皮肿瘤（TETs）是由胸腺瘤和胸腺癌组成的罕见肿瘤。需要新的治疗方法，尤其是在胸腺癌中，其 5 年生存率徘徊在 30%左右。间皮素（MSLN）是一种表面糖蛋白，可被切割产生成熟的 MSLN（mMSLN）和巨核细胞促进因子（MPF），仅在有限的组织中表达。然而，它在各种癌症中都有表达，包括胸腺癌，其中 79%的病例都有表达。
我们利用流式细胞术、体外细胞毒性测定和体内异种移植模型，证明了间皮素靶向抗体药物偶联物（ADC）anetumab ravtansine（ARav）抑制胸腺癌生长的能力。
胸腺瘤和胸腺癌细胞系表达 MSLN，anetumab 是 ARav 的抗体部分，能够结合表达 MSLN 的胸腺癌细胞并内化。ARav 能有效抑制体外稳定转染 mMSLN 的胸腺癌细胞的生长。在体内，15mg/kg 的 ARav 抑制了 T1889 异种移植肿瘤的生长，而将 7.5mg/kg 的 ARav 与 4mg/kg 的顺铂联合使用对抑制肿瘤生长具有相加作用。
这些数据表明，anetumab ravtansine 可抑制体外和体内 MSLN 阳性胸腺癌细胞的生长。
