2024-01-04 スイス連邦工科大学ローザンヌ校(EPFL)
◆Nature Biotechnologyに発表された研究により、治療の長期的な有効性が示され、製造が迅速でコスト効果が高い可能性が浮かび上がった。これにより、がん患者に対する効果的なCAR-T療法が進化し、低コストで利用可能になる可能性があります。
<関連情報>
- https://actu.epfl.ch/news/supercharging-car-t-cells-for-cancer-treatment-2/
- https://www.nature.com/articles/s41587-023-02060-8
IL-10を発現するCAR T細胞は機能障害に抵抗し、固形腫瘍や転移巣の持続的なクリアランスを媒介する IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases
Yang Zhao,Jiangqing Chen,Massimo Andreatta,Bing Feng,Yu-Qing Xie,Mathias Wenes,Yi Wang,Min Gao,Xiaomeng Hu,Pedro Romero,Santiago Carmona,Jie Sun,Yugang Guo & Li Tang
Nature Biotechnology Published:02 January 2024
DOI:https://doi.org/10.1038/s41587-023-02060-8
Abstract
The success of chimeric antigen receptor (CAR) T cell therapy in treating several hematopoietic malignancies has been difficult to replicate in solid tumors, in part because of T cell exhaustion and eventually dysfunction. To counter T cell dysfunction in the tumor microenvironment, we metabolically armored CAR T cells by engineering them to secrete interleukin-10 (IL-10). We show that IL-10 CAR T cells preserve intact mitochondrial structure and function in the tumor microenvironment and increase oxidative phosphorylation in a mitochondrial pyruvate carrier-dependent manner. IL-10 secretion promoted proliferation and effector function of CAR T cells, leading to complete regression of established solid tumors and metastatic cancers across several cancer types in syngeneic and xenograft mouse models, including colon cancer, breast cancer, melanoma and pancreatic cancer. IL-10 CAR T cells also induced stem cell-like memory responses in lymphoid organs that imparted durable protection against tumor rechallenge. Our results establish a generalizable approach to counter CAR T cell dysfunction through metabolic armoring, leading to solid tumor eradication and long-lasting immune protection.
