9IUT

Crystal structure of cancer-specific anti-HER2 antibody H2Mab-250 in complex with epitope peptide

9IUT の概要

• エントリーDOI: 10.2210/pdb9iut/pdb
• 分子名称: H2Mab-250 VH(S112C)-SARAH, H2Mab-250 VL-SARAH(S37C), H2Mab-250 epitope peptide, ... (4 entities in total)
• 機能のキーワード: fv-clasp, antibody, cancer-specific, her2, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 77962.30

構造登録者

Arimori, T.,Takagi, J. (登録日: 2024-07-22, 公開日: 2025-06-04, 最終更新日: 2025-07-16)

主引用文献

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, 32:1087-1101.e4, 2025

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: 40472844
DOI: 10.1016/j.stem.2025.05.007

実験手法

X-RAY DIFFRACTION (2.09 Å)