肿瘤细胞治疗研究
英文原题：Rationally designed approaches to augment CAR-T therapy for solid tumor treatment.
Rationally designed approaches to augment CAR-T therapy for solid tumor treatment.
被称为 CAR-T 疗法的CAR-T 细胞疗法，已在 B 细胞恶性肿瘤治疗中取得令人惊叹的治疗进展。
CAR-T（CAR-T）疗法已在B细胞恶性肿瘤中取得非凡进展，但在实体瘤中尚未成功实现疗效。与血液癌症不同，实体瘤具有血管失调、细胞外基质致密和免疫抑制信号丰富等特征，导致CAR-T细胞浸润不足并迅速功能障碍。肿瘤细胞识别不足及肿瘤异质性最终会导致癌症复发。此外，CAR-T治疗还有安全性问题，包括潜在细胞因子释放风暴、“靶向肿瘤但伤及正常组织”毒性和神经系统副作用。本文全面回顾多个靶向层面，包括CAR-T细胞设计、肿瘤调节和递送策略。研究者认为，应通过构建优化CAR-T细胞、直接调节肿瘤组织微环境并选择最合适的递送策略，合理设计联合CAR-T疗法，以兼顾安全性和疗效。
Chimeric antigen receptor T cell denoted as CAR-T therapy has realized incredible therapeutic advancements for B cell malignancy treatment. However, its therapeutic validity has yet to be successfully achieved in solid tumors. Different from hematological cancers, solid tumors are characterized by dysregulated blood vessels, dense extracellular matrix, and filled with immunosuppressive signals, which together result in CAR-T cells' insufficient infiltration and rapid dysfunction. The insufficient recognition of tumor cells and tumor heterogeneity eventually causes cancer reoccurrences. In addition, CAR-T therapy also raises safety concerns, including potential cytokine release storm, on-target/off-tumor toxicities, and neuro-system side effects. Here we comprehensively review various targeting aspects, including CAR-T cell design, tumor modulation, and delivery strategy. We believe it is essential to rationally design a combinatory CAR-T therapy via constructing optimized CAR-T cells, directly manipulating tumor tissue microenvironments, and selecting the most suitable delivery strategy to achieve the optimal outcome in both safety and efficacy.
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