CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
体内生成 CAR-T 细胞以治疗肿瘤与自身免疫性疾病
英文原题：In vivo CAR T cell generation to treat cancer and autoimmune disease.
查看英文原题
In vivo CAR T cell generation to treat cancer and autoimmune disease.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法已改变了B细胞恶性肿瘤的治疗。然而，其更广泛的应用受到复杂制造过程和淋巴细胞清除化疗必要性的限制，制约了患者的可及性。我们提出了一种体内工程化策略，利用靶向脂质纳米颗粒（tLNPs）将信使RNA递送至特定T细胞亚群。这些tLNPs在健康供者和自身免疫患者样本中重编程了CD8+ T细胞，体内给药在人源化小鼠中实现了肿瘤控制，并在食蟹猴中导致B细胞耗竭。在食蟹猴中，耗竭后重建的B细胞主要为na ve细胞，提示免疫系统重置。通过消除对复杂体外制造的需求，该tLNP平台有望使CAR-T 细胞疗法更易获得，并适用于更多临床适应症。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapies have transformed treatment of B cell malignancies.
However, their broader application is limited by complex manufacturing processes and the necessity for lymphodepleting chemotherapy, restricting patient accessibility.
We present an in vivo engineering strategy using targeted lipid nanoparticles (tLNPs) for messenger RNA delivery to specific T cell subsets. These tLNPs reprogrammed CD8 + T cells in both healthy donor and autoimmune patient samples, and in vivo dosing resulted in tumor control in humanized mice and B cell depletion in cynomolgus monkeys.
In cynomolgus monkeys, the reconstituted B cells after depletion were predominantly na ve, suggesting an immune system reset. By eliminating the requirements for complex ex vivo manufacturing, this tLNP platform holds the potential to make CAR T cell therapies more accessible and applicable across additional clinical indications.
论文信息
- 作者
- Hunter TL、Bao Y、Zhang Y、Matsuda D、Riener R、Wang A、Li JJ、Soldevila F
- 单位
- Capstan Therapeutics, San Diego, CA, USA.United States
- 文献类型
- 美国 NIH 院内研究 · 非美国政府资助研究
- 期刊
- Science (New York, N.Y.)2025 Jun 19
- 原文标识
- PubMed 40536974 · DOI 10.1126/science.ads8473