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
英文原题:Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment.
Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment.
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免疫细胞衔接器(ICEs)是一类新兴的免疫疗法,旨在通过精确靶向和激活免疫效应细胞来利用免疫系统的抗肿瘤潜力。通过衔接T细胞、自然杀伤(NK)细胞和吞噬细胞,ICEs克服了免疫逃逸和MHC下调等挑战,解决了癌症治疗中的关键障碍。以双特异性T细胞衔接器(BiTEs)为代表的T细胞衔接器(TCEs)在该领域占据主导地位,半衰期延长的BiTEs、三特异性抗体和检查点抑制性T细胞衔接器等创新推动了其在血液恶性肿瘤和实体瘤中的应用。NK细胞衔接器(NKCEs)和吞噬细胞衔接器(PCEs)正在快速发展,利用NK细胞的固有细胞毒性和巨噬细胞的吞噬能力来靶向肿瘤,尤其是在免疫抑制微环境中。自2014年FDA批准Blinatumomab以来,ICEs已改变了肿瘤学格局,目前已有九个FDA批准的产品和众多候选药物处于临床试验中。尽管面临毒性、耐药性和实体瘤中疗效有限等挑战,对先进平台和联合疗法的持续研究凸显了ICEs在提供个性化、可扩展且有效的癌症治疗方面日益增长的潜力。本综述探讨了ICEs的机制、平台、研究趋势和临床进展,强调其在推进精准免疫治疗中的关键作用及其作为下一代癌症疗法基石的潜力。
Immune cell engagers (ICEs) are an emerging class of immunotherapies designed to harness the immune system's anti-tumor potential through precise targeting and activation of immune effector cells. By engaging T cells, natural killer (NK) cells, and phagocytes, ICEs overcome challenges such as immune evasion and MHC downregulation, addressing critical barriers in cancer treatment. T-cell engagers (TCEs), led by bispecific T-cell engagers (BiTEs), dominate the field, with innovations such as half-life-extended BiTEs, trispecific antibodies, and checkpoint inhibitory T-cell engagers driving their application in hematologic and solid malignancies. NK cell engagers (NKCEs) and phagocyte cell engagers (PCEs) are rapidly progressing, drawing on NK cells' innate cytotoxicity and macrophages' phagocytic abilities to target tumors, particularly in immunosuppressive microenvironments.
Since the FDA approval of Blinatumomab in 2014, ICEs have transformed the oncology landscape, with nine FDA-approved products and numerous candidates in clinical trials. Despite challenges such as toxicity, resistance, and limited efficacy in solid tumors, ongoing research into advanced platforms and combination therapies highlights the growing potential of ICEs to provide personalized, scalable, and effective cancer treatments.
This review investigates the mechanisms, platforms, research trends, and clinical progress of ICEs, emphasizing their pivotal role in advancing precision immunotherapy and their promise as a cornerstone of next-generation cancer therapies.
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