皮下からCAR-T細胞療法を促進する(Boosting CAR-T cell therapies from under the skin)

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2024-06-14 ハーバード大学

CAR-T細胞療法は、治癒困難な血液癌の治療に革命をもたらしていますが、効果は部分的なものが多く、新しい治療戦略が必要です。ハーバード大学の研究チームは、CAR-T細胞を再刺激するために皮下に注入できる生分解性の足場材料(T細胞強化足場、TES)を開発しました。マウスを使った実験では、TESがCAR-T細胞の数を増やし、腫瘍細胞を殺す能力を高めることが確認されました。この発見は、CAR-T細胞療法の効果を向上させ、製造プロセスの一部を患者の体内で行うことで治療を簡素化する可能性を示しています。

<関連情報>

投与前のCAR-T細胞の抗腫瘍活性を再刺激するための皮下生分解性足場 Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells

David K. Y. Zhang,Joshua M. Brockman,Kwasi Adu-Berchie,Yutong Liu,Yoav Binenbaum,Irene de Lázaro,Miguel C. Sobral,Rea Tresa & David J. Mooney
Nature Biomedical Engineering  Published:03 June 2024
DOI:https://doi.org/10.1038/s41551-024-01216-4

皮下からCAR-T細胞療法を促進する(Boosting CAR-T cell therapies from under the skin)

Abstract

The efficacy of adoptive T-cell therapies based on chimaeric antigen receptors (CARs) is limited by the poor proliferation and persistence of the engineered T cells. Here we show that a subcutaneously injected biodegradable scaffold that facilitates the infiltration and egress of specific T-cell subpopulations, which forms a microenvironment mimicking features of physiological T-cell activation, enhances the antitumour activity of pre-administered CAR-T cells. CAR-T-cell expansion, differentiation and cytotoxicity were driven by the scaffold’s incorporation of co-stimulatory bound ligands and soluble molecules, and depended on the types of co-stimulatory molecules and the context in which they were presented. In mice with aggressive lymphoma, a single, local injection of the scaffold following non-curative CAR-T-cell dosing led to more persistent memory-like T cells and extended animal survival. Injectable biomaterials with optimized ligand presentation may boost the therapeutic performance of CAR-T-cell therapies.

医療・健康
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