RocRock Biotechnology Co. Ltd, Suzhou, China.
Joint Laboratory of Biomaterials and Translational Medicine, Puheng Technology Co., Ltd, Suzhou, China.
Commun Biol. 2024 Oct 11;7(1):1302. doi: 10.1038/s42003-024-07009-4.
Chimeric antigen receptor (CAR) T-cell therapies have shown remarkable results in patients with hematological malignancies. However, their success in treating solid tumors has been limited. As an alternative candidate for the CAR therapy, CAR-macrophages (CAR-M) have demonstrated activation and phagocytosis directed by tumor-associated antigen (TAA), showing promise in the treatment of solid tumors. Nevertheless, the mechanisms by which CARs direct tumor chemotaxis and invasion of CAR-M remain poorly understood. In this study, we aim to investigate the role of CARs in CAR-M attachment and infiltration using 3D tumor spheroids, which were created by utilizing a novel self-assembling nucleic acid nanostructure decorated living cells (NAC). Our results demonstrated that CAR-M exhibited higher invasion and killing capacity in 2D model and 3D tumor spheroids. In summary, the 3D NAC assembled tumor spheroid model provides a suitable platform for target screening and pharmacodynamic evaluation of CAR-M.
嵌合抗原受体 (CAR) T 细胞疗法在血液系统恶性肿瘤患者中显示出显著的疗效。然而，它们在治疗实体瘤方面的效果有限。作为 CAR 治疗的另一种候选物，CAR 巨噬细胞 (CAR-M) 已被证明可被肿瘤相关抗原 (TAA) 激活和吞噬，在治疗实体瘤方面具有广阔的前景。然而，CAR 引导 CAR-M 趋化和浸润肿瘤的机制仍知之甚少。在这项研究中，我们旨在使用 3D 肿瘤球体来研究 CAR 在 CAR-M 黏附和浸润中的作用，该 3D 肿瘤球体是利用一种新型自组装核酸纳米结构修饰的活细胞 (NAC) 构建的。我们的结果表明，CAR-M 在 2D 模型和 3D 肿瘤球体中表现出更高的侵袭和杀伤能力。总之，3D NAC 组装的肿瘤球体模型为 CAR-M 的靶向筛选和药效评估提供了一个合适的平台。
