9MTE
CryoEM structure of extracellular domain of human HER2 complexed with two nano-bodies 27A05 and 47D05
Summary for 9MTE
| Entry DOI | 10.2210/pdb9mte/pdb |
| EMDB information | 48606 |
| Descriptor | VHH nanobody 27A05, VHH nanobody 47D05, Receptor tyrosine-protein kinase erbB-2 (3 entities in total) |
| Functional Keywords | nanobodies, vhh, her2, complex, cancer, transferase, transferase-immune system complex, transferase/immune system |
| Biological source | Lama glama (llama) More |
| Total number of polymer chains | 3 |
| Total formula weight | 99473.90 |
| Authors | Bruch, E.M.,Rak, A. (deposition date: 2025-01-11, release date: 2025-11-19, Last modification date: 2026-01-21) |
| Primary citation | De Tavernier, E.,Kim, P.S.,Bruch, E.M.,Cortez-Retamozo, V.F.,Timmerman, L.,Flynn, A.L.,Van Overbeke, W.,Tirode, F.,Cintra Barbosa-Lorenzi, V.,Piepenhagen, P.,Dinh-Le, T.,Luna, E.,Li, A.,Baker, A.,Rak, A.,Pao, L.I.,Vintem, A.P.B. TPP-45142-an Anti-HER2 T cell Engager-Designed for Selective HER2-Low Cancer Immunotherapy. Mol.Cancer Ther., 2026 Cited by PubMed Abstract: The standard of care for patients with HER2-positive cancers is well established, but a significant unmet need exists for patients with HER2-low tumors, who do not meet the eligibility criteria for trastuzumab, and for patients with HER2-positive tumors, who are refractory to trastuzumab treatment. Therefore, in this study, we developed a NANOBODY® domain-based HER2-targeting, T cell receptor (TCR)αβ-based T cell engager (TCE) molecule-TPP-45142; it recognizes a HER2 epitope distinct from that recognized by trastuzumab and pertuzumab and redirects T cells to kill HER2-low cancers such as breast, gastric, and gastroesophageal junction adenocarcinoma (GEJ) cancers. TPP-45142 mediated potent T cell-dependent cytotoxicity against HER2-low cancer cell lines in vitro and inhibited in vivo tumor growth of HER2-low breast cancer xenografts. TPP-45142 was highly selective toward tumor cells expressing low HER2 levels than toward normal cardiac cells and exhibited a favourable therapeutic index as per a cytokine release assay. Thus, TPP-45142, with an improved safety profile, is a promising next-generation TCE for treating challenging HER2-low cancers. PubMed: 41504346DOI: 10.1158/1535-7163.MCT-25-0654 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.66 Å) |
Structure validation
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