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:From benchside avatars to bedside breakthroughs: Patient-derived organoids in the new era of cancer immunotherapy.
From benchside avatars to bedside breakthroughs: Patient-derived organoids in the new era of cancer immunotherapy.
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癌症免疫疗法的成功受到缺乏能够预测患者特异性反应并指导新型疗法开发的动态模型的阻碍。静态生物标志物,如 PD-L1 表达和肿瘤突变负荷,往往无法捕捉肿瘤-免疫对话的复杂性。患者来源的肿瘤类器官(PDTOs)已成为一种革命性的 ex vivo 平台,弥合了这一差距。本综述概述了 PDTOs 从简单的上皮培养物到复杂的、具有免疫能力的“化身”的演变,这些“化身”忠实地再现了患者的肿瘤微环境(TME)。
我们批判性地讨论了重建 TME 的关键方法,包括与多种免疫细胞和基质细胞(如 T 细胞、MDSCs、CAFs、中性粒细胞)的“添加式”共培养系统,以及保留天然免疫生态系统的“一体化”方法。
此外,我们强调了这些先进模型在预测检查点抑制剂疗效之外的扩展作用。我们展示了它们作为下一代免疫疗法核心开发平台的突破性应用,包括 CAR-T 细胞疗法和个性化新抗原疫苗的验证。在承认仍然存在重大转化挑战的同时,我们得出结论:具有免疫能力的 PDTOs 代表了一种不可或缺的工具,有望加速精准免疫肿瘤学新时代的到来。
The success of cancer immunotherapy is hampered by the lack of dynamic models that can predict patient-specific responses and guide the development of novel treatments. Static biomarkers, such as PD-L1 expression and tumor mutational burden, often fail to capture the complexity of the tumor-immune dialogue.
Patient-derived tumor organoids (PDTOs) have emerged as a revolutionary ex vivo platform that bridges this gap. This review outlines the evolution of PDTOs from simple epithelial cultures to sophisticated, immune-competent "avatars" that faithfully recapitulate the patient's tumor microenvironment (TME).
We critically discuss the key methodologies for reconstructing the TME, including "add-in" co-culture systems with diverse immune and stromal cells (e. g. , T-cells, MDSCs, CAFs, neutrophils) and "all-in-one" approaches that preserve the native immune ecosystem.
Furthermore, we highlight the expanding role of these advanced models beyond predicting checkpoint inhibitor efficacy.
We showcase their groundbreaking applications as core development platforms for next-generation immunotherapies, including CAR-T cell therapy and the validation of personalized neoantigen-based vaccines. While acknowledging the significant translational challenges that remain, we conclude that immune-competent PDTOs represent an indispensable tool poised to accelerate the new era of precision immuno-oncology.
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