Yang Chunli, Zhao Wei, Zhang Li, He Liming, Wang Siyi, Wang Jie, Xiang Maya, Yuan Xin, Gou Maling
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, #17 Section 3, Renmin South Road, Chengdu, Sichuan Province, 610041, China.
Department of Oncology, West China Hospital, Sichuan University, #37 Guoxue Alley, Wuhou District, Chengdu, Sichuan Province, 610041, China.
Adv Healthc Mater. 2025 Jan;14(1):e2400678. doi: 10.1002/adhm.202400678. Epub 2024 Nov 5.
The living tumor cell vaccine (TCV) holds a promise for cancer immunotherapy. Microneedle arrays provide a tool to improve the immune response of vaccines by the intradermal administration in a painless manner. However, it remains challenges for microneedle arrays to deliver the living TCV intradermally. Here, an ice microneedle array delivered living TCVs is shown with sustained granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion for cancer treatment. The ice microneedle array is composed of ice microneedles and a matching polymer holder, which are customized fabricated by a static optical projection lithography (SOPL) technique. The living TCV consisted of irradiated melanoma cells transfected with nanoparticle-mediated GM-CSF plasmids. After the living TCV is readily loaded into the ice microneedle via a cryopreservation process, it could be efficiently delivered into the dermis by the microneedle device. Compared to the subcutaneous injection, intradermal administration led to the recruitment of more dendritic cells at the vaccination site and the increased infiltration of CD8 T cells in the tumor. The ice microneedle array deliveres intradermal TCVs significantly inhibited melanoma growth and effectively prevented melanoma recurrence without obvious side effects. This work demonstrates a promising TCVs for melanoma treatment, which will inspire the future of cancer immunotherapy.
活肿瘤细胞疫苗（TCV）在癌症免疫治疗方面具有前景。微针阵列提供了一种通过无痛皮内给药来改善疫苗免疫反应的工具。然而，微针阵列将活TCV皮内给药仍面临挑战。在此，展示了一种能递送活TCV并持续分泌粒细胞巨噬细胞集落刺激因子（GM-CSF）用于癌症治疗的冰微针阵列。该冰微针阵列由冰微针和配套的聚合物支架组成，它们通过静态光学投影光刻（SOPL）技术定制制造。活TCV由用纳米颗粒介导的GM-CSF质粒转染的经辐照黑色素瘤细胞组成。在通过冷冻保存过程将活TCV轻松加载到冰微针中后，它可以通过微针装置有效地递送至真皮。与皮下注射相比，皮内给药导致接种部位募集更多树突状细胞，并增加肿瘤中CD8 T细胞的浸润。冰微针阵列递送皮内TCV显著抑制黑色素瘤生长，并有效预防黑色素瘤复发，且无明显副作用。这项工作展示了一种用于黑色素瘤治疗的有前景的TCV，这将为癌症免疫治疗的未来带来启发。
