<br>使用特异于 Brevican 去糖基化亚型的新型肽靶向胶质母细胞瘤,Advanced Therapeutics

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使用特异于 Brevican 去糖基化亚型的新型肽靶向胶质母细胞瘤
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2021-01-20 , DOI: 10.1002/adtp.202000244
Niklas von Spreckelsen _{1,

2,

3} , Colin M Fadzen ₂ , Nina Hartrampf _{2,

4} , Yarah Ghotmi ₁ , Justin M Wolfe ₂ , Shipra Dubey ₅ , Bo Yeun Yang ₅ , Marie F Kijewski ₅ , Shuyan Wang ₅ , Charlotte Farquhar ₂ , Sonja Bergmann ₁ , Mykola Zdioruk ₁ , J Roscoe Wasserburg ₁ , Benjamin Scott ₁ , Emily Murrell ₆ , Fernanda C Bononi ₆ , Leonard G Luyt ₆ , Marcelo DiCarli ₅ , Martine L M Lamfers ₇ , Keith L Ligon ₈ , E Antonio Chiocca ₁ , Mariano S Viapiano ₉ , Bradley L Pentelute ₂ , Sean E Lawler ₁ , Choi-Fong Cho _{1,

2}

Affiliation

Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Department of Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital, University of Cologne, 50937 Cologne, Germany.
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA02115, United States.
Department of Chemistry, University of Western Ontario, London, ON N6C 4K3 Canada.
Department of Neurosurgery, Brain Tumor Center, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Pathology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, New York 13210.

胶质母细胞瘤（GBM）是最常见和最致命的脑肿瘤形式，并且仍然是最难治疗的癌症之一。 Brevican (Bcan) 是一种中枢神经系统 (CNS) 特异性细胞外基质蛋白，在包括 GBM 在内的高级胶质瘤细胞中表达上调。缺乏大部分糖基化的 Bcan 亚型 dg-Bcan 仅存在于 GBM 组织中。在这里，dg-Bcan 被探索作为 GBM 的分子靶标。在这项研究中，筛选了d肽库，以鉴定一种小的 8 氨基酸 dg- B can-靶向肽(BTP) 候选物，称为 BTP-7，它以高亲和力和特异性结合 dg-Bcan。 BTP-7 优先被表达 dg-Bcan 的患者来源的 GBM 细胞内化。为了证明 GBM 靶向，BTP-7 用¹⁸ F（一种氟放射性同位素）进行放射性标记，并且使用正电子发射断层扫描 (PET) 成像在小鼠中建立的颅内 GBM 中发现放射性示踪剂积累增加。 dg-Bcan 是 GBM 的一个有吸引力的分子靶标，而 BTP-7 代表了进一步开发新型成像剂和靶向治疗的有希望的主要候选药物。

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更新日期：2021-01-20

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