肿瘤细胞治疗研究
英文原题：CRISPR/Cas9 in cancer therapy: clinical translation, mechanistic strategies, and therapeutic directions.
CRISPR/Cas9基因组编辑技术的出现，通过促进对疾病相关遗传修饰的精确和可编程操控，显著改变了癌症治疗领域的格局。
CRISPR/Cas9基因组编辑的出现通过促进对疾病相关遗传改变的精确和可编程操控，显著改变了癌症治疗的格局。本综述通过分析已发表的文献和注册临床试验，全面评估了基于CRISPR/Cas9的癌症疗法的当前临床和转化 landscape。目前CRISPR/Cas9在肿瘤学中的应用主要集中在三种机制策略：增强肿瘤识别的免疫细胞工程、直接靶向致癌突变以及调节肿瘤支持性通路。对32项临床试验的分析表明，基于CRISPR的干预已显示出令人鼓舞的安全性特征和早期临床活性迹象，尤其是在ex vivo工程化免疫细胞疗法中。值得注意的例子包括靶向CD19和BCMA的CRISPR编辑CAR-T细胞产品，这些产品在复发或难治性血液系统恶性肿瘤中实现了客观缓解，同时显示出编辑细胞在体内的持续存留。相比之下，由于递送效率、肿瘤异质性和免疫抑制性肿瘤微环境相关的挑战，向实体瘤的临床转化仍然相对有限。技术进步，包括多重基因组编辑、碱基编辑和先导编辑，扩展了基于CRISPR干预的精确性和多功能性，同时与免疫疗法和基于纳米技术的递送系统的整合继续拓宽治疗潜力。尽管取得了这些进展，仍有若干重大挑战需要解决，包括脱靶编辑、生产可扩展性、递送局限性和监管考量。总体而言，CRISPR/Cas9 在肿瘤学中代表了一个有前景但仍在不断发展的平台，其未来的临床成功取决于在精准性、安全性、可扩展性和长期治疗持久性之间取得平衡。
The advent of CRISPR/Cas9 genome editing has significantly transformed the landscape of cancer therapeutics by facilitating precise and programmable manipulation of disease-associated genetic modifications. This review comprehensively evaluates the current clinical and translational landscape of CRISPR/Cas9-based cancer therapies through an analysis of published literature and registered clinical trials. The current CRISPR/Cas9 applications in oncology are primarily centred on three mechanistic strategies: immune cell engineering for enhanced tumor recognition, direct targeting of oncogenic mutations, and modulation of tumor-supportive pathways. Analysis of 32 clinical trials indicates that CRISPR-based interventions have demonstrated encouraging safety profiles and early signs of clinical activity, particularly in ex vivo engineered immune-cell therapies. Notable examples include CRISPR-edited CAR-T cell products targeting CD19 and BCMA , which have achieved objective responses in relapsed or refractory hematological malignancies while demonstrating sustained persistence of edited cells in vivo . In contrast, clinical translation into solid tumors remains comparatively limited due to challenges associated with delivery efficiency, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Technological advancements, including multiplex genome editing, base editing, and prime editing have expanded the precision and versatility of CRISPR-based interventions, while integration with immunotherapy and nanotechnology-based delivery systems continues to broaden therapeutic potential. Despite these advances, several significant challenges still need to be addressed, including off-target editing, manufacturing scalability, delivery limitations, and regulatory considerations. Overall, CRISPR/Cas9 represents a promising yet evolving platform in oncology, with its future clinical success dependent on achieving a balance between precision, safety, scalability, and long-term therapeutic durability.
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