دورية أكاديمية
Generation of a Novel SORT1×HER2 Bispecific Antibody–Drug Conjugate Targeting HER2-Low-Expression Tumor
| العنوان: | Generation of a Novel SORT1×HER2 Bispecific Antibody–Drug Conjugate Targeting HER2-Low-Expression Tumor |
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| المؤلفون: | Weiliang Zhuang, Wei Zhang, Lei Wang, Liping Xie, Jun Feng, Baohong Zhang, Youjia Hu |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 22, p 16056 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | SORT1, HER2 targeted, bispecific antibody–drug conjugate, internalization, tumor inhibition, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Human epidermal growth factor receptor 2 (HER2) is considered an ideal antibody–drug conjugate (ADC) target because the gene is overexpressed in many tumors compared to normal tissues. Multiple anti-HER2 ADCs conjugated with different toxic payloads bring benefits to patients with high HER2 expression. However, HER2-targeted ADC technology needs further optimization to improve its effect for the treatment of patients with low HER2 expression. We hypothesized that bispecific antibody–drug conjugate (bsADC) targeting HER2 and Sortilin-1 (SORT1) would overcome this limitation. SORT1 is a suitable target for pairing with HER2 to generate a bispecific antibody (BsAb) since the gene is co-expressed with HER2 in tumors and possesses rapid internalization. We developed a BsAb (bsSORT1×HER2) that exhibited strong binding and internalization activity on HER2-low-expression tumor cells and facilitated higher HER2 degradation. The bsSORT1×HER2 was further conjugated with DXd to generate a bsADC (bsSORT1×HER2-DXd) that showed strong cytotoxicity on HER2-low-expression tumor cells and antitumor efficacy in an MDA-MB-231 xenograft mice model. These results demonstrated that employment of a SORT1×HER2-targeted bsADC may be promising to improve the antitumor efficacy of HER2-targeted ADC for the treatment of tumors with low HER2 expression. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/22/16056; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms242216056 |
| URL الوصول: | https://doaj.org/article/745088049e0e4f48a8f0057c59db8437 |
| رقم الأكسشن: | edsdoj.745088049e0e4f48a8f0057c59db8437 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms242216056 |