Preparation and anti-tumor activity of a novel antibody-drug conjugate 607-LDM
10.16438/j.0513-4870.2020-1225
- VernacularTitle:新型抗体偶联药物607-LDM的制备及抗肿瘤活性研究
- Author:
Qun YU
1
;
Jia-lu YUAN
2
,
3
;
Xiao-tian ZHAI
1
;
Jian MA
2
,
3
;
Qing-fang MIAO
1
;
Yong-su ZHEN
1
Author Information
1. NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
2. National Engineering Research Center of Antibody Medicine, Shanghai 201203, China
3. Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
antibody-drug conjugate;
human epidermal growth factor receptor 2;
lidamycin;
ovarian cancer;
breast cancer;
anti-tumor activity
- From:
Acta Pharmaceutica Sinica
2021;56(2):496-502
- CountryChina
- Language:Chinese
-
Abstract:
Antibody-drug conjugates (ADCs) are one of the most important classes of anticancer therapeutics. Human epidermal growth factor receptor-2 (HER2), which is highly expressed in many types of aggressive cancers including breast and ovarian cancer, has been approved as an ideal target for ADCs. Lidamycin (LDM), developed by Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, is an enediyne-containing antibiotic with potent anti-tumor activity. LDM is a promising payload for ADCs. In the present research, using a special site-directed conjugating technology, we made a novel ADC (607-LDM) with a drug-to-antibody ratio (DAR) of 2 and composed of the anti-HER2 antibody 607 and LDM. The new ADC exhibited potent antitumor activity against human ovarian cancer SKOV3 and breast cancer BT-474 cells. It also induced apoptosis and G2/M arrest. In nude mice with SKOV3 xenografts and a tumor volume of 150-200 mm3, a single intravenous injection 607-LDM at 1 mg·kg-1 induced tumor growth inhibition of 72.4%, which was significant compared to either LDM (50.6%) or antibody (30.2%) treatment alone, or both in combination (50.1%, P < 0.05). All animal experiments were performed in accord with National Regulations and approved by the Animal Experiments Ethical Committee of College of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. The novel ADC designed in this study, 607-LDM, is a promising candidate for the treatment of HER2-positive cancers.
