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:AI-driven cellular immunotherapy: transforming CAR-T engineering and translation.
AI-driven cellular immunotherapy: transforming CAR-T engineering and translation.
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CAR-T(CAR-T)细胞疗法在血液系统恶性肿瘤中取得了显著成功,但在实体瘤治疗和更广泛的临床转化方面仍面临持续挑战,包括靶点特异性有限、肿瘤抗原表达异质、功能结果难以预测以及生产流程复杂。人工智能(AI)的最新进展正开始改变应对这些挑战的方式,使数据驱动的设计、预测和优化能够贯穿CAR-T 研发的整个流程。在这篇综述中,我们考察了机器学习、深度学习和生成模型等现代AI方法如何重塑CAR-T 工程化的关键环节。首先,我们讨论整合多组学和临床数据集、用于识别肿瘤特异性靶点的AI辅助抗原发现策略。随后,我们考察AI赋能的抗原识别模块工程化,包括抗体来源和TCR来源结合结构域的计算设计与优化。接着,我们介绍利用AI模型设计CAR结构和合成信号回路的新兴研究。
我们还综述了AI辅助预测CAR-T 功能表现、治疗疗效和临床结局的进展。最后,我们讨论AI在生产、质量控制和流程优化中的日益重要作用,包括基于图像的细胞表型分析,以及对生产流程的数字化监测。
综上,这些进展表明,CAR-T 工程化正从经验驱动转向可编程、可预测且日益自主的设计框架,有望加快开发更安全、更有效的细胞免疫疗法。
Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable success in hematologic malignancies but faces persistent challenges in solid tumors and broader clinical translation, including limited target specificity, heterogeneous tumor antigen expression, unpredictable functional outcomes, and complex manufacturing processes.
Recent advances in artificial intelligence (AI) are beginning to transform how these challenges are addressed by enabling data-driven design, prediction, and optimization across the entire CAR-T development pipeline. In this review, we examine how modern AI approaches such as machine learning, deep learning, and generative models are reshaping key stages of CAR-T engineering.
We first discuss AI-assisted antigen discovery strategies that integrate multi-omics and clinical datasets to identify tumor-specific targets.
We then examine AI-enabled engineering of antigen-recognition modules, including computational design and optimization of antibody- and TCR-derived binding domains. Next, we highlight emerging efforts to program CAR architectures and synthetic signaling circuits using AI models.
We further review AI-assisted prediction of CAR-T functional performance, therapeutic efficacy, and clinical outcomes.
Finally, we discuss the growing role of AI in manufacturing, quality control, and process optimization, including image-based cellular phenotyping and digital monitoring of production pipelines.
Together, these advances suggest a shift from empirical CAR-T engineering toward programmable, predictive, and increasingly autonomous design frameworks that may accelerate the development of safer and more effective cellular immunotherapies.
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