9IUT
Crystal structure of cancer-specific anti-HER2 antibody H2Mab-250 in complex with epitope peptide
Summary for 9IUT
| Entry DOI | 10.2210/pdb9iut/pdb |
| Descriptor | H2Mab-250 VH(S112C)-SARAH, H2Mab-250 VL-SARAH(S37C), H2Mab-250 epitope peptide, ... (4 entities in total) |
| Functional Keywords | fv-clasp, antibody, cancer-specific, her2, immune system |
| Biological source | Mus musculus More |
| Total number of polymer chains | 6 |
| Total formula weight | 77962.30 |
| Authors | Arimori, T.,Takagi, J. (deposition date: 2024-07-22, release date: 2025-06-04, Last modification date: 2025-06-18) |
| Primary citation | Hosking, M.P.,Shirinbak, S.,Omilusik, K.,Chandra, S.,Kaneko, M.K.,Gentile, A.,Yamamoto, S.,Shrestha, B.,Grant, J.,Boyett, M.,Cardenas, D.,Keegan, H.,Ibitokou, S.,Pavon, C.,Mizoguchi, T.,Ihara, T.,Nakayama, D.,Abujarour, R.,Lee, T.T.,Clarke, R.,Goodridge, J.,Peralta, E.,Maeda, T.,Takagi, J.,Arimori, T.,Kato, Y.,Valamehr, B. Preferential tumor targeting of HER2 by iPSC-derived CAR T cells engineered to overcome multiple barriers to solid tumor efficacy. Cell Stem Cell, 2025 Cited by PubMed Abstract: Chimeric antigen receptor (CAR) T cell therapies in solid tumors have been limited by on-target, off-tumor toxicity, antigen heterogeneity, and an inability to simultaneously overcome multiple diverse resistance mechanisms within the tumor microenvironment that attenuate anti-tumor activity. Here, we describe an induced pluripotent stem cell (iPSC)-derived CAR T cell that combines a human epidermal growth factor receptor 2 (HER2)-targeting CAR-differentially recognizing tumor from normal cells and enabling detection of both truncated and misfolded HER2-with multiplex editing designed to address and overcome obstacles to maximize efficacy in solid tumor indications. The iPSC-derived, HER2-directed CAR T cells maintained potent HER2-specific anti-tumor activity in both in vitro and in vivo settings, with limited cytolytic targeting of HER2+ normal targets. Combination with therapeutic antibodies enabled comprehensive multi-antigen targeting through both the CAR and a high-affinity, non-cleavable CD16a Fc receptor. Additionally, specific engineering of interleukin (IL)-7R-fusion, transforming growth factor β (TGF-β)-IL-18R, and CXCR2 enabled sustained persistence, resistance to TGF-β-mediated suppression, and specific migration to the tumor. PubMed: 40472844DOI: 10.1016/j.stem.2025.05.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.09 Å) |
Structure validation
Download full validation report
