RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CAR 工程化非常规 T 细胞的临床前景
英文原题：The clinical landscape of CAR-engineered unconventional T cells.
查看英文原题
The clinical landscape of CAR-engineered unconventional T cells.
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中文摘要
非常规T细胞，如恒定自然杀伤T（iNKT）细胞、γδ T细胞和黏膜相关恒定T（MAIT）细胞，在连接固有免疫和适应性免疫中发挥关键作用。它们快速靶向肿瘤和有效调节肿瘤微环境（TME）的能力使其成为癌症免疫治疗的有前景的候选者。嵌合抗原受体（CAR）工程的进展进一步凸显了其治疗潜力，特别是在治疗具有挑战性的癌症方面。值得注意的是，这些细胞表现出良好的安全性特征，增强了其作为现货型治疗选择的可行性。我们全面分析了CAR工程化非常规T细胞的临床应用，重点关注遗传修饰、生产工艺、预处理方案和给药策略。我们讨论了近期临床试验中的成功案例，并探索了利用这些细胞进行癌症治疗及其他应用的未来方向。
展开英文摘要原文
Unconventional T cells, such as invariant natural killer T (iNKT), γδ T, and mucosal-associated invariant T (MAIT) cells, play a pivotal role in bridging innate and adaptive immunity. Their capacity for rapid tumor targeting and effective modulation of the tumor microenvironment (TME) makes them promising candidates for cancer immunotherapy. Advances in chimeric antigen receptor (CAR) engineering have further highlighted their therapeutic potential, particularly for treating challenging cancers.
Notably, these cells exhibit favorable safety profiles, enhancing their viability as off-the-shelf therapeutic options.
We provide a comprehensive analysis of the clinical applications of CAR-engineered unconventional T cells, focusing on genetic modifications, manufacturing processes, preconditioning regimens, and dosing strategies.
We discuss successful examples from recent clinical trials and explore future directions for utilizing these cells in cancer therapy and beyond.
论文信息
- 作者
- Li YR、Zhu Y、Chen Y、Yang L
- 第一作者单位
- Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: charlie.li@ucla.edu.United States
- 通讯作者单位
- Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: liliyang@ucla.edu.United States
- 文献类型
- 综述
- 期刊
- Trends in cancer2025 Jun
- 原文标识
- PubMed 40155286 · DOI 10.1016/j.trecan.2025.03.001