8P2E

Homotypic interacting B1 fab bound to Chondroitin Sulfate A

8P2E の概要

• エントリーDOI: 10.2210/pdb8p2e/pdb
• EMDBエントリー: 17362
• 分子名称: B1 fab light, B1 fab heavy (2 entities in total)
• 機能のキーワード: chondroitin sulfate a, sugar binding protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 200327.50

構造登録者

Raghavan, S.S.R.,Dagil, R.,Wang, K.T.,Salanti, A. (登録日: 2023-05-16, 公開日: 2024-06-05, 最終更新日: 2025-07-02)

主引用文献

Vidal-Calvo, E.E.,Martin-Salazar, A.,Choudhary, S.,Dagil, R.,Raghavan, S.S.R.,Duvnjak, L.,Nordmaj, M.A.,Clausen, T.M.,Skafte, A.,Oberkofler, J.,Wang, K.,Agerbaek, M.O.,Loppke, C.,Jorgensen, A.M.,Ropac, D.,Mujollari, J.,Willis, S.,Garcias Lopez, A.,Miller, R.L.,Karlsson, R.T.G.,Goerdeler, F.,Chen, Y.H.,Colaco, A.R.,Wang, Y.,Lavstsen, T.,Martowicz, A.,Nelepcu, I.,Marzban, M.,Oo, H.Z.,Orum-Madsen, M.S.,Wang, Y.,Nielsen, M.A.,Clausen, H.,Wierer, M.,Wolf, D.,Gogenur, I.,Theander, T.G.,Al-Nakouzi, N.,Gustavsson, T.,Daugaard, M.,Salanti, A.
Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.
Nat Commun, 15:7553-7553, 2024

PubMed Abstract: Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.

PubMed: 39215044
DOI: 10.1038/s41467-024-51781-0

実験手法

ELECTRON MICROSCOPY (3.2 Å)