| Autor: |
Fang‐Zheng Qi, Hui‐Shan Su, Bo Wang, Luo‐Meng Qian, Yang Wang, Chen‐Hui Wang, Ya‐Xin Hou, Ping Chen, Qing Zhang, Dong‐Mei Li, Hao Tang, Jian‐Li Jiang, Hui‐Jie Bian, Zhi‐Nan Chen, Si‐He Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
MedComm, Vol 5, Iss 3, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2688-2663 |
| DOI: |
10.1002/mco2.512 |
| Popis: |
Abstract Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on‐target off‐tumor toxicity limits Ab‐based therapeutics. Cluster of differentiation 147 (CD147) is a tumor‐associated membrane antigen overexpressed in cancer cells. Ab‐based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia‐activation strategies, we developed a conditional Ab‐dependent cellular cytotoxicity (ADCC)‐enhanced humanized anti‐CD147 Ab, HcHAb18‐azo‐PEG5000 (HAP18). Afucosylated ADCC‐enhanced HcHAb18 Ab was produced by a fed‐batch cell culture system. Azobenzene (Azo)‐linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia‐responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement‐dependent cytotoxicity, and Ab‐dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor‐inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia‐activated ADCC‐enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti‐CD147 Ab drugs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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