| Autor: |
Huiling Wang, Yiming Li, Gang Shi, Yuan Wang, Yi Lin, Qin Wang, Yujing Zhang, Qianmei Yang, Lei Dai, Lin Cheng, Xiaolan Su, Yang Yang, Shuang Zhang, Zhi Li, Jia Li, Yuquan Wei, Dechao Yu, Hongxin Deng |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Oncolytics, Vol 16, Iss , Pp 20-29 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2372-7705 |
| DOI: |
10.1016/j.omto.2019.12.004 |
| Popis: |
Therapeutic antibodies targeting vascular endothelial growth factor (VEGF) have become a critical regimen for tumor therapy, but the efficacy of monotherapy is usually limited by drug resistance and multiple angiogenic mechanisms. Complement proteins are becoming potential candidates for cancer-targeted therapy based on their role in promoting cancer progression and angiogenesis. However, the antitumor abilities of simultaneous VEGF and complement blockade were unknown. We generated a humanized soluble VEGFR-Fc fusion protein (VID) binding VEGFA/PIGF and a CR1-Fc fusion protein (CID) targeting C3b/C4b. Both VID and CID had good affinities to their ligands and showed effective bioactivities. In vitro, angiogenesis effects induced by VEGF and hemolysis induced by complement were inhibited by VID and CID, respectively. Further, VID and CID confer a synergetic therapeutic effect in a colitis-associated colorectal cancer (CAC) model and an orthotopic 4T1 breast cancer model. Mechanically, combination therapy inhibited tumor angiogenesis, cell proliferation, and MDSC infiltration in the tumor microenvironment and promoted tumor cell apoptosis. Our study offers a novel therapeutic strategy for anti-VEGF-resistant tumors and chronic-inflammation-associated tumors. Keywords: VEGFR-Fc fusion protein, CR1-Fc fusion protein, combination therapy, angiogenesis, MDSCs |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
