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:Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy.
Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy.
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在癌症免疫治疗领域,一场深刻的演进催生了复杂的策略,涵盖传统癌症疫苗和新兴病毒疫苗。这篇综合性综述深入探讨了这些方法的技术路线、临床应用、成功案例和未来前景。传统癌症疫苗利用蛋白质、多肽和树突状细胞等多种形式取得了重大进展。较新的创新聚焦于使人体能够识别和对抗癌前及恶性细胞的生理机制,引入了特异性标志物,如靶向肿瘤相关抗原的多肽抗癌疫苗。
此外,癌症病毒疫苗利用工程化病毒刺激针对特定抗原的免疫反应,在诱导强效且持久的免疫方面展现出巨大前景。与单克隆抗体、佐剂和放射治疗等互补治疗方法的整合,不仅提高了生存率,还加深了我们对病毒毒力的理解。疫苗设计的最新进展,包括溶瘤病毒、病毒样颗粒和病毒载体,标志着创新的前沿。尽管这些进展具有巨大潜力,但仍需解决关键挑战,如免疫逃逸策略、潜在的脱靶效应以及病毒基因组的优化。在免疫治疗的格局中,值得关注的创新从使用免疫调节剂增强固有免疫和适应性免疫协作中脱颖而出。蛋白水解靶向嵌合体(PROTACs)作为癌症治疗的精准工具的出现尤其令人振奋。本综述聚焦于从黑色素瘤到难治性实体瘤等多种癌症,批判性地评估了癌症疫苗的类型、机制、疫苗治疗中的障碍、疫苗效力、安全性特征以及免疫相关不良事件,并就涉及细胞毒性T细胞、NK 细胞和树突状细胞的潜在机制提供了细致入微的视角。本综述还强调了临床研究、分子测序和人工智能等前沿技术在推动癌症疫苗领域发展方面的变革性潜力。这些工具不仅加速了进展,也凸显了该研究的多维性和快速演变特性,印证了其在癌症治疗更广泛背景下的深远意义。
In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches.
Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens.
Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration.
The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells.
The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy.
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