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| 001 | 154523 | ||
| 005 | 20240229123106.0 | ||
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| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Singhal, Mahak |0 P:(DE-He78)1956b17ee4a34a5fdd72287aca7cdc0a |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody. |
| 260 | _ | _ | |a Heidelberg |c 2020 |b EMBO Press |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1600862641_5630 |2 PUB:(DE-HGF) |
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| 520 | _ | _ | |a The angiopoietin (Ang)-Tie pathway has been intensely pursued as candidate second-generation anti-angiogenic target. While much of the translational work has focused on the ligand Ang2, the clinical efficacy of Ang2-targeting drugs is limited and failed to improve patient survival. In turn, the orphan receptor Tie1 remains therapeutically unexplored, although its endothelial-specific genetic deletion has previously been shown to result in a strong reduction in metastatic growth. Here, we report a novel Tie1 function-blocking antibody (AB-Tie1-39), which suppressed postnatal retinal angiogenesis. During primary tumor growth, neoadjuvant administration of AB-Tie1-39 strongly impeded systemic metastasis. Furthermore, the administration of AB-Tie1-39 in a perioperative therapeutic window led to a significant survival advantage as compared to control-IgG-treated mice. Additional in vivo experimental metastasis and in vitro transmigration assays concurrently revealed that AB-Tie1-39 treatment suppressed tumor cell extravasation at secondary sites. Taken together, the data phenocopy previous genetic work in endothelial Tie1 KO mice and thereby validate AB-Tie1-39 as a Tie1 function-blocking antibody. The study establishes Tie1 as a therapeutic target for metastasis in a perioperative or neoadjuvant setting. |
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| 700 | 1 | _ | |a Gengenbacher, Nicolas |0 P:(DE-He78)d2851af71b2aced0c34d8c71329c3bc5 |b 1 |e First author |u dkfz |
| 700 | 1 | _ | |a La Porta, Silvia |0 P:(DE-He78)b8f19c256fc9d795781f1e0c6e7c5c6d |b 2 |e First author |
| 700 | 1 | _ | |a Gehrs, Stephanie |0 P:(DE-He78)6c7c0079533d7a9cda3bb9f463e22ccb |b 3 |u dkfz |
| 700 | 1 | _ | |a Shi, Jingjing |0 P:(DE-He78)585602d04403479b3a3146ea350520f1 |b 4 |u dkfz |
| 700 | 1 | _ | |a Kamiyama, Miki |0 P:(DE-He78)96a15fcb74f3594a17c47e0a70aa9ccd |b 5 |u dkfz |
| 700 | 1 | _ | |a Bodenmiller, Diane M |b 6 |
| 700 | 1 | _ | |a Fischl, Anthony |b 7 |
| 700 | 1 | _ | |a Schieb, Benjamin |0 P:(DE-He78)1f150c2a39cb02fbf582905920fa0ec2 |b 8 |u dkfz |
| 700 | 1 | _ | |a Besemfelder, Eva |0 P:(DE-He78)9be9200416a88a73cc9c25339b19b58f |b 9 |u dkfz |
| 700 | 1 | _ | |a Chintharlapalli, Sudhakar |b 10 |
| 700 | 1 | _ | |a Augustin, Hellmut |0 P:(DE-He78)2e92d0ae281932fc7347d819fec36b0b |b 11 |e Last author |u dkfz |
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