CAR-X工学戦略と細胞治療応用を体系的にレビュー(HUANG He and HU Yongxian’s team systematically review CAR-X engineering strategies and applications as a new paradigm in cell therapy)

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2026-06-16 浙江大学(ZJU)

浙江大学医学院附属第一病院および良渚実験室の黄河教授、胡永先教授らは、CAR-T細胞以外の免疫細胞にCAR(キメラ抗原受容体)技術を適用する「CAR-X細胞工学」について体系的に整理し、その設計戦略と応用展望をNature Reviews Bioengineering誌で総説として発表した。CAR-Xは、CAR-NK細胞、CARマクロファージ(CAR-Mac)、CAR制御性T細胞(CAR-Treg)、CAR-iNKT細胞、CAR-γδT細胞、CAR-MAIT細胞などを総称する概念である。従来のCAR-T療法が抱える固形腫瘍への浸潤不足、抗原逃避、T細胞疲弊などの課題に対し、各免疫細胞が持つ固有機能を活用して克服を目指す。例えばCAR-NKは高い安全性と汎用製品化に適し、CAR-Macは腫瘍微小環境の改変能力を有し、CAR-Tregは自己免疫疾患や移植片対宿主病に対する標的免疫抑制を実現できる。さらにiPSC由来細胞やCRISPR遺伝子編集技術を利用した製造法、細胞種ごとに最適化したCAR設計も解説された。CAR-Xは血液がんに加え、固形がん、自己免疫疾患、移植医療など幅広い疾患領域への応用が期待される次世代細胞治療プラットフォームとして注目されている。

CAR-X工学戦略と細胞治療応用を体系的にレビュー(HUANG He and HU Yongxian’s team systematically review CAR-X engineering strategies and applications as a new paradigm in cell therapy)
Figure 1 Generic functional properties of distinct CAR-X cells

<関連情報>

CAR-X細胞工学 CAR-X cell engineering

Xia Li  (李侠),Haikun Lin  (林海坤),Jiehan Liang  (梁捷翰),Xin Jin  (金鑫),Tingfeng Shen  (沈庭峰),Yongxian Hu  (胡永仙) & He Huang  (黄河)
Nature Reviews Bioengineering  Published:27 April 2026
DOI:https://doi.org/10.1038/s44222-026-00430-w

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of haematological malignancies and continues to transform the treatment of various other diseases. Nonetheless, current CAR-T cell therapy has limitations that hinder its therapeutic efficacy for expanded applications, some of which might be attributed to intrinsic T cell features. Using immune cells beyond conventional T cells has therefore emerged as a promising strategy to compensate for such limitations. In this Review, we discuss different CAR-engineered immune cells for therapeutic applications by highlighting how unique immune attributes, along with cell-specific manufacturing strategies and CAR designs, address challenges faced by conventional CAR-T cell therapy.

Key points

  • Limitations of conventional chimeric antigen receptor (CAR)-T cells, including exhaustion, antigen heterogeneity and poor solid tumour infiltration, have driven the development of alternative CAR-engineered immune cell (CAR-X cell) platforms.
  • CAR-X cell platforms leverage lineage-specific immunobiology, such as innate cytotoxicity, tissue tropism, immune regulation or reduced alloreactivity, to overcome functional constraints inherent to conventional T cells.
  • CAR-X cell therapy efficacy requires lineage-tailored CAR designs and manufacturing strategies, including cell sourcing, expansion protocols and gene editing compatibility, which collectively determine scalability and translational robustness.
  • Early clinical evaluations of CAR-natural killer cell, CAR-macrophage, CAR-regulatory T cell and CAR-natural killer T cell therapies demonstrate feasibility and distinct therapeutic benefits, including reduced inflammatory toxicity, reduced alloreactive risks or targeted immune suppression.
  • The therapeutic efficacy of CAR-X cell therapies depends on persistence, scalable manufacturing and safety control, alongside deeper mechanistic understanding to enable lineage-tailored next-generation CAR engineering.
細胞遺伝子工学
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