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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune Organoids: A Review of Their Applications in Cancer and Autoimmune Disease Immunotherapy.
Immune Organoids: A Review of Their Applications in Cancer and Autoimmune Disease Immunotherapy.
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免疫类器官已成为免疫学领域的突破性平台,可在生理相关且可控的环境中模拟人类免疫应答并评估免疫治疗策略。此类三维结构由干细胞或原代组织构建,能够重现淋巴组织结构、细胞多样性和功能动态的关键特征,相比传统二维培养和动物模型更为准确。免疫类器官可模拟复杂免疫微环境,因此在癌症免疫治疗开发、自身免疫性疾病建模和个体化医疗中处于前沿。本叙述性综述介绍免疫类器官技术的进展,重点讨论其在检测免疫检查点抑制剂、CAR-T 细胞和癌症疫苗等免疫疗法中的应用。文章还探讨免疫类器官如何助力研究自身免疫性疾病发病机制及其分子基础,并支持高通量药物筛选。尽管潜力巨大,免疫类器官仍面临多项挑战,包括难以复现全身性免疫相互作用、构建流程标准化不足、规模化受限、生物学异质性,以及缺乏血管化(限制类器官体积和成熟度)。未来方向包括将免疫类器官与多器官系统整合以更好模拟全身生理、开发更接近淋巴组织细胞外基质的先进生物材料、引入人工智能(AI)优化类器官制备和数据分析,以及严格开展类器官研究结果的临床验证。持续创新和跨学科合作对于克服现有障碍至关重要,将推动免疫类器官广泛应用于免疫治疗、疫苗开发和精准医疗。
Immune organoids have emerged as a ground-breaking platform in immunology, offering a physiologically relevant and controllable environment to model human immune responses and evaluate immunotherapeutic strategies. Derived from stem cells or primary tissues, these three-dimensional constructs recapitulate key aspects of lymphoid tissue architecture, cellular diversity, and functional dynamics, providing a more accurate alternative to traditional two-dimensional cultures and animal models. Their ability to mimic complex immune microenvironments has positioned immune organoids at the forefront of cancer immunotherapy development, autoimmune disease modeling, and personalized medicine. This narrative review highlights the advances in immune organoid technology, with a focus on their applications in testing immunotherapies, such as checkpoint inhibitors, CAR-T cells, and cancer vaccines. It also explores how immune organoids facilitate the study of autoimmune disease pathogenesis with insights into their molecular basis and support in high-throughput drug screening.
Despite their transformative potential, immune organoids face significant challenges, including the replication of systemic immune interactions, standardization of fabrication protocols, scalability limitations, biological heterogeneity, and the absence of vascularization, which restricts organoid size and maturation.
Future directions emphasize the integration of immune organoids with multi-organ systems to better replicate systemic physiology, the development of advanced biomaterials that closely mimic lymphoid extracellular matrices, the incorporation of artificial intelligence (AI) to optimize organoid production and data analysis, and the rigorous clinical validation of organoid-derived findings.
Continued innovation and interdisciplinary collaboration will be essential to overcome existing barriers, enabling the widespread adoption of immune organoids as indispensable tools for advancing immunotherapy, vaccine development, and precision medicine.
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