Matsunaga Yuki, Yamaoka Toshimitsu, Ohba Motoi, Miura Sakiko, Masuda Hiroko, Sangai Takafumi, Takimoto Masafumi, Nakamura Seigo, Tsurutani Junji
Department of Breast Surgical Oncology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Antibodies (Basel). 2021 Feb 1;10(1):6. doi: 10.3390/antib10010006.
Antibody-drug conjugates (ADCs), which are currently being developed, may become promising cancer therapeutics. Folate receptor α (FOLR1), a glycosylphosphatidylinositol-anchored membrane protein, is an attractive target of ADCs, as it is largely absent from normal tissues but is overexpressed in malignant tumors of epithelial origin, including ovarian, lung, and breast cancer. In this study, we tested the effects of novel anti-FOLR1 antibody-eribulin conjugate MORAb-202 in breast cancer and non-small cell lung cancer (NSCLC) cell lines. FOLR1 expression, cell proliferation, bystander killing effects, and apoptosis were evaluated in seven breast cancer and nine NSCLC cell lines treated with MORAb-202. Tumor growth and FOLR1 expression were assessed in T47D and MCF7 orthotopic xenograft mouse models after a single intravenous administration of MORAb-202 (5 mg/kg). MORAb-202 was associated with inhibited cell proliferation, with specific selectivity toward FOLR1-expressing breast cancer cell lines. Eribulin, the payload of MORAb-202, was unleashed in HCC1954 cells, diffused into intercellular spaces, and then killed the non-FOLR1-expressing MCF7 cells in co-culture systems. In orthotopic xenograft mouse models, FOLR1-expressing T47D tumors and non-FOLR1-expressing MCF7 tumors were suppressed upon MORAb-202 administration. The novel anti-FOLR1 antibody-eribulin conjugate MORAb-202 has potential antitumor effects in breast cancer.
目前正在研发的抗体药物偶联物（ADCs）可能会成为有前景的癌症治疗药物。叶酸受体α（FOLR1）是一种糖基磷脂酰肌醇锚定膜蛋白，是ADC的一个有吸引力的靶点，因为它在正常组织中基本不存在，但在上皮来源的恶性肿瘤中过表达，包括卵巢癌、肺癌和乳腺癌。在本研究中，我们测试了新型抗FOLR1抗体-艾瑞布林偶联物MORAb-202对乳腺癌和非小细胞肺癌（NSCLC）细胞系的作用。在用MORAb-202处理的7种乳腺癌和9种NSCLC细胞系中评估了FOLR1表达、细胞增殖、旁观者杀伤效应和细胞凋亡。在单次静脉注射MORAb-202（5mg/kg）后，在T47D和MCF7原位异种移植小鼠模型中评估肿瘤生长和FOLR1表达。MORAb-202与细胞增殖受抑制有关，对表达FOLR1的乳腺癌细胞系具有特异性选择性。MORAb-202的有效载荷艾瑞布林在HCC1954细胞中释放，扩散到细胞间隙，然后在共培养系统中杀死不表达FOLR1的MCF7细胞。在原位异种移植小鼠模型中，给予MORAb-202后，表达FOLR1的T47D肿瘤和不表达FOLR1的MCF7肿瘤均受到抑制。新型抗FOLR1抗体-艾瑞布林偶联物MORAb-202在乳腺癌中具有潜在的抗肿瘤作用。
