論文 - 詳細
| RRC ID | 89441 |
|---|---|
| 著者 | Baker DJ, Frommer LM, Uslu U, Patel KK, Zhu D, Engel NW, George JM, Zhao W, Kim SI, Sun L, Roselle C, Rommel PC, Young RM, Epstein JA, Hayat S, Arany Z, June CH. |
| タイトル | AI-driven discovery of GPNMB CAR T cells as a multi-cancer therapy. |
| ジャーナル | Cell |
| Abstract |
Chimeric antigen receptor (CAR) T cells have demonstrated curative potential in hematologic cancers and increasing efficacy in solid tumors and non-malignant diseases. However, target identification remains a major bottleneck. We developed an artificial intelligence (AI)-driven approach for CAR T cell target discovery by integrating single-cell RNA sequencing datasets from human skin cancer and healthy tissue. Candidates were refined using public datasets to optimize for tumor composition, tissue specificity, and clinical feasibility. Large language models were applied to prioritize and nominate targets with therapeutic promise. Glycoprotein non-metastatic melanoma protein B (GPNMB) was the most frequently nominated target. We validated its expression across hematologic and solid tumors. We engineered a human GPNMB-directed CAR T cell, which showed potent anti-tumor activity in mouse models of monoblastic leukemia, melanoma, and colorectal adenocarcinoma. These findings establish a scalable pipeline for CAR T cell target discovery and support the translation of GPNMB-directed CAR T cells as a multi-cancer therapeutic. |
| 巻・号 | 189(13) |
| ページ | 3871-3882.e12 |
| 公開日 | 2026-6-25 |
| DOI | 10.1016/j.cell.2026.06.002 |
| PII | S0092-8674(26)00651-3 |
| PMID | 42349383 |
| MeSH | Animals Cell Line, Tumor Humans Immunotherapy, Adoptive* / methods Intelligent Systems Melanoma / immunology Melanoma / therapy Membrane Glycoproteins* / genetics Membrane Glycoproteins* / immunology Membrane Glycoproteins* / metabolism Mice Neoplasms* / immunology Neoplasms* / therapy Receptors, Chimeric Antigen* / immunology Receptors, Chimeric Antigen* / metabolism Skin Neoplasms / immunology Skin Neoplasms / therapy T-Lymphocytes* / immunology |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 123 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 110.4 |
| リソース情報 | |
| ヒト・動物細胞 | KLM-1(RCB2138) |