CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, P.R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Adv Mater. 2024 Oct;36(40):e2407525. doi: 10.1002/adma.202407525. Epub 2024 Aug 20.
Adoptive cell therapy (ACT) has shown great success in the clinic for treating hematologic malignancies. However, solid tumor treatment with ACT monotherapy is still challenging, owing to insufficient expansion and rapid exhaustion of adoptive cells, tumor antigen downregulation/loss, and dense tumor extracellular matrix. Delivery strategies for combination cell therapy have great potential to overcome these hurdles. The delivery of vaccines, immune checkpoint inhibitors, cytokines, chemotherapeutics, and photothermal reagents in combination with adoptive cells, have been shown to improve the expansion/activation, decrease exhaustion, and promote the penetration of adoptive cells in solid tumors. Moreover, the delivery of nucleic acids to engineer immune cells directly in vivo holds promise to overcome many of the hurdles associated with the complex ex vivo cell engineering strategies. Here, these research advance, as well as the opportunities and challenges for integrating delivery technologies into cell therapy s are discussed, and the outlook for these emerging areas are criticlly analyzed.
过继细胞疗法（ACT）在治疗血液恶性肿瘤的临床应用中取得了巨大成功。然而，由于过继细胞的扩增不足和快速耗竭、肿瘤抗原下调/丢失以及致密的肿瘤细胞外基质，ACT 单药治疗实体瘤仍然具有挑战性。联合细胞疗法的递送策略具有克服这些障碍的巨大潜力。与过继细胞联合递送疫苗、免疫检查点抑制剂、细胞因子、化疗药物和光热试剂已被证明可以提高过继细胞的扩增/激活、减少耗竭，并促进其在实体瘤中的渗透。此外，将核酸直接递送到体内工程化免疫细胞有望克服与复杂的体外细胞工程策略相关的许多障碍。在这里，讨论了这些研究进展，以及将递送技术整合到细胞疗法中的机遇和挑战，并对这些新兴领域进行了批判性分析。
