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:Bispecific and multispecific immune engagers for redirecting innate and adaptive immunity against hematologic cancers.
Bispecific and multispecific immune engagers for redirecting innate and adaptive immunity against hematologic cancers.
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双特异性抗体(BsAbs)和多特异性抗体(MsAbs)代表了一类具有变革意义的肿瘤免疫治疗药物。这些工程化分子具有独特的能力,可同时靶向两种或多种不同抗原,从而促进精准的免疫细胞衔接并干扰多条信号通路。这篇综合性综述聚焦于它们在重定向固有免疫(NK 细胞、吞噬细胞)和适应性免疫(T 细胞)中的关键作用,尤其着重于其在血液系统恶性肿瘤中的应用。显著的临床成功,例如 FDA 批准 blinatumomab 等药物,凸显了这些疗法对患者结局产生的深远影响。尽管前景广阔,固有挑战依然存在,包括管理治疗相关毒性、克服肿瘤耐药机制以及优化药代动力学特征。然而,正在进行的研究仍在持续推动创新策略以应对这些障碍,凸显了免疫衔接器在未来提供更个性化、可规模化且高度有效的癌症治疗方面的巨大潜力。
Bispecific antibodies (BsAbs) and multispecific antibodies (MsAbs) represent a transformative class of immunotherapeutics in oncology. These engineered molecules possess the unique ability to simultaneously target two or more distinct antigens, thereby facilitating precise immune cell engagement and disrupting multiple signaling pathways. This comprehensive review focuses on their pivotal role in redirecting both innate (natural killer cells, phagocytes) and adaptive (T cells) immunity, with a particular emphasis on their application against hematologic cancers.
Significant clinical successes, exemplified by the FDA approval of agents such as blinatumomab, underscore the profound impact these therapies have had on patient outcomes. Despite their promise, inherent challenges persist, including managing treatment-related toxicities, overcoming tumor resistance mechanisms, and optimizing pharmacokinetic profiles.
Ongoing research, however, continues to drive innovative strategies to address these hurdles, highlighting the immense potential of immune engagers to deliver more personalized, scalable, and highly effective cancer treatments in the future.
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