Antitumor effect of a novel humanized MUC1 antibody-drug conjugate on triple-negative breast cancer

被引：1
作者：
Li, Lan [1 ]
Cao, Jiawei [2 ]
Chen, Chunyan [2 ]
Qin, Yaqian [3 ]
He, Licai [2 ]
Gu, Haihua [2 ]
Wu, Guang [2 ]
机构：
[1] Wenzhou Med Univ, Sch Publ Hlth & Management, Wenzhou 325035, Peoples R China
[2] Wenzhou Med Univ, Sch Lab Med & Life Sci, Wenzhou Key Lab Canc Pathogenesis & Translat, Key Lab Lab Med,Minist Educ, Wenzhou 325035, Peoples R China
[3] Wenzhou Med Univ, Med Res Ctr, Affiliated Hosp 1, Wenzhou 325000, Peoples R China
来源：
HELIYON | 2023年 / 9卷 / 04期
基金：
中国国家自然科学基金;
关键词：
Mucin1; Humanized antibody; Antibody -drug conjugate; MMAE; TNBC; MUCINS;
D O I：
10.1016/j.heliyon.2023.e15164
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Breast cancer is the most common malignant cancer in women. Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes and is challenging to treat. MUC1 is a ther-apeutic target in breast and pancreatic cancer. We developed a novel humanized antibody that specifically binds MUC1 expressed in breast cancer cells and conjugated a humanized MUC1 (HzMUC1) antibody to monomethyl auristatin (MMAE). HzMUC1-MMAE showed an anti -proliferative effect on HER2 positive trastuzumab-resistant breast cancer. Immunoprecipitation indicated that HzMUC1 recognized native MUC1 in TNBC cells. Confocal microscopy showed that HzMUC1 bound MUC1 on the surface of TNBC cells, and the conjugates exhibited the same binding ability to HCC70 as unconjugated HzMUC1 by cell-based ELISA. Treatment of TNBC cells with HzMUC1-MMAE reduced growth of MUC1-positive cells and induced G2/M cell cycle arrest and apoptosis. In a mouse model of breast cancer, HzMUC1-MMAE significantly reduced the growth of tumors established by subcutaneous injection of HCC70 TNBC cells. Therefore, HzMUC1-ADC has therapeutic potential for TNBC.
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页数：9
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