글로벌 연구동향
분자영상 및 방사화학
- 2017년 12월호
[Mol Pharm.] Targeted Cancer Therapy Using Fusion Protein of TNFα and Tumor-Associated Fibronectin-Specific Aptide.한국세라믹,KAIST/ 전형수, 김성현*, 전상용*
- 출처
- Mol Pharm.
- 등재일
- 2017 Nov 6
- 저널이슈번호
- 14(11):3772-3779. doi: 10.1021/acs.molpharmaceut.7b00520. Epub 2017 Oct 11.
- 내용
Abstract
Tumor necrosis factor-α has shown potent antitumor effects in preclinical and clinical studies. However, severe side effects at less than therapeutic doses have limited its systemic delivery, prompting the need for a new strategy for targeted delivery of the protein to tumors. Here, we report a fusion protein of mouse tumor necrosis factor (TNF)-α (mTNFα) and a cancer-targeting, high-affinity aptide and investigate its therapeutic efficacy in tumor-bearing mice. A fusion protein consisting of mTNFα, a linker, and an aptide specific to extra domain B (EDB) of fibronectin (APTEDB), designated mTNFα-APTEDB, was successfully produced by expression in Escherichia coli. mTNFα-APTEDB retained specificity and affinity for its target, EDB. In mice bearing EDB-overexpressing fibrosarcomas, mTNFα-APTEDB showed greater efficacy in inhibiting tumor growth than mTNFα alone or mTNFα linked to a nonrelevant aptide, without causing an appreciable loss in body weight. Moreover, in vivo antitumor efficacy was further significantly increased by combination treatment with the chemotherapeutic drug, melphalan, suggesting a synergistic effect attributable to enhanced drug uptake into the tumor as a result of TNFα-mediated enhanced vascular permeability. These results suggest that a fusion protein of mTNFα with a cancer-targeting peptide could be a new anticancer therapeutic option for ensuring potent antitumor efficacy after systemic delivery.
Author informationJeon H, Kim D, Choi M, Kang S, Kim JY, Kim S1, Jon S.
1
Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology , 202 Osongsaengmyeong 1-ro, Cheongjusi 28160, Chungcheongbuk-do, South Korea.
- 키워드
- aptides; cancer therapy; combination therapy; extra domain B of fibronectin; tumor necrosis factor α
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