CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Next-generation oncology: integrative therapeutic frontiers at the crossroads of precision genomics, immuno-engineering, and tumor microenvironment modulation.
Next-generation oncology: integrative therapeutic frontiers at the crossroads of precision genomics, immuno-engineering, and tumor microenvironment modulation.
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肿瘤学正经历范式转变,从传统细胞毒性疗法转向整合式、智能驱动的框架,结合精准基因组学、免疫工程和肿瘤微环境(TME)调节。本综述将癌症视为复杂适应系统(CAS),探讨其如何通过遗传、表观遗传和微环境相互作用不断演变,并因此需要动态、多维的治疗策略。综述指出单靶点疗法的局限,以及协同策略的兴起,包括人工智能指导的自适应给药、合成生物学增强型CAR-T 细胞和TME代谢重编程。分子制图、量子生物学、合成肿瘤学及暗基因组挖掘方面的突破正在拓展治疗前沿。与此同时,免疫工程创新——如新一代检查点调节剂、逻辑门控CAR-T 细胞和新抗原疫苗——正在重塑肿瘤免疫学。靶向TME的策略,包括基质重塑、缺氧调节和微生物组工程,也有助于克服治疗耐药。多组学分析、联合治疗和计算肿瘤学(如数字孪生)的融合,正推动实时个体化干预。尽管取得这些进展,治疗耐药、毒性、可及性和伦理问题仍然存在,需要跨学科合作和公平创新。未来方向是发展适应性、自主化肿瘤治疗,整合人工智能、闭环疗法及模块化mRNA平台,以规模化提供精准医疗。本综述强调,应采用统一的系统性方法,将癌症转变为可管理的疾病。
The landscape of oncology is undergoing a paradigm shift, transitioning from conventional cytotoxic therapies to an integrative, intelligence-driven framework that combines precision genomics, immunoengineering, and modulation of the tumor microenvironment (TME). This review explores how cancer, as a complex adaptive system (CAS), evolves through genetic, epigenetic, and microenvironmental interactions, necessitating dynamic, multi-dimensional therapeutic strategies.
Review highlights the limitations of mono-targeted therapies and the emergence of synergistic approaches, including AI-guided adaptive dosing, synthetic biology-enhanced CAR-T cells, and metabolic reprogramming of the tumor microenvironment (TME). Breakthroughs in molecular cartography, quantum biology, synthetic oncology, and dark genome mining are expanding therapeutic frontiers. Meanwhile, immuno-engineering innovations-such as next-generation checkpoint modulators, logic-gated CAR-T cells, and neoantigen vaccines-are redefining immune-oncology.
Additionally, TME-targeted strategies, including stromal remodeling, hypoxia modulation, and microbiome engineering, are helping to overcome treatment resistance. The convergence of multi-omics profiling, combinatorial therapeutics, and computational oncology (e. g. , digital twins) is enabling real-time, personalized interventions.
Despite these advances, challenges persist-therapeutic resistance, toxicity, accessibility, and ethical concerns-demanding interdisciplinary collaboration and equitable innovation. The future lies in adaptive, autonomous oncology, integrating AI, closed-loop therapies, and modular mRNA platforms to deliver precision medicine at scale. This review underscores the imperative for a unified, systems-based approach to transform cancer into a manageable condition.
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