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:Harnessing cytokine immunocomplexes and cytokine fusion proteins for cancer Therapy: Mechanisms and clinical potential.
Harnessing cytokine immunocomplexes and cytokine fusion proteins for cancer Therapy: Mechanisms and clinical potential.
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细胞因子是细胞功能和免疫反应的关键调节因子,使其成为癌症免疫治疗中极具前景的靶点。尽管细胞因子免疫治疗已广泛应用于临床,但其疗效常受限于多效性作用、半衰期短、生物分布不均以及高剂量下的严重副作用。近年来细胞因子生物学的进展促进了细胞因子-抗体免疫复合物和细胞因子融合蛋白的开发,为癌症治疗提供了新范式。这些创新增强了细胞因子选择性激活特定靶向癌症的免疫细胞群(如 CD8 T 细胞和 NK 细胞)的能力,有效抑制肿瘤进展。此外,这两种治疗策略均可减轻全身毒性并延长细胞因子在体内的生物活性。本综述深入探讨了细胞因子免疫复合物和细胞因子融合蛋白的最新进展,特别聚焦于正处于临床/临床前开发阶段的 IL-2、IL-7 和 IL-15。此外,我们讨论了这些策略在近期临床前和临床研究中观察到的治疗获益,以及为充分释放其在癌症免疫治疗中的潜力所必须应对的挑战。
Cytokines are pivotal regulators of cellular functions and immune responses, making them highly promising targets for cancer immunotherapy. Despite their widespread clinical application, the effectiveness of cytokine immunotherapy is often hampered by their pleiotropic effects, short half-lives, uneven biodistribution, and severe side effects at high dosages.
Recent advancements in cytokine biology have led to the development of cytokine-antibody immunocomplexes and cytokine fusion proteins, offering a new paradigm in cancer treatments. These innovations foster the ability of cytokines to selectively activate specific cancer-targeting immune cell populations, such as CD8 T cells and NK cells, effectively inhibiting tumour progression.
Furthermore, both therapeutic approaches can mitigate systemic toxicities and prolong the biological activity of cytokines in the body. This review delves into the recent advancements of cytokine immunocomplexes and cytokine fusion proteins, with a particular focus on interleukin-2 (IL-2), IL-7 and IL-15, which are in clinical/preclinical development.
Moreover, we discuss the therapeutic benefits of these approaches observed in recent preclinical and clinical studies, along with the challenges that must be addressed to fully unlock their potential in cancer immunotherapy.
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