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通过冰微针进行皮内细胞疫苗递送用于癌症治疗

Intradermal Delivery of Cell Vaccine via Ice Microneedles for Cancer Treatment.

作者信息

Yang Chunli, Zhao Wei, Zhang Li, He Liming, Wang Siyi, Wang Jie, Xiang Maya, Yuan Xin, Gou Maling

机构信息

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.

出版信息

Adv Healthc Mater. 2025 Jan;14(1):e2400678. doi: 10.1002/adhm.202400678. Epub 2024 Nov 5.


DOI:10.1002/adhm.202400678
PMID:39499079
Abstract

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.

摘要

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。

相似文献

[1]
Intradermal Delivery of Cell Vaccine via Ice Microneedles for Cancer Treatment.

Adv Healthc Mater. 2025-1

[2]
Ice-pop making inspired photothermal ultra-swelling microneedles to facilitate loading and intradermal vaccination of tumor antigen.

J Control Release. 2025-3-10

[3]
Intradermal delivery of vaccine nanoparticles using hollow microneedle array generates enhanced and balanced immune response.

J Control Release. 2018-12-17

[4]
Phase I/IB study of immunization with autologous tumor cells transfected with the GM-CSF gene by particle-mediated transfer in patients with melanoma or sarcoma.

Hum Gene Ther. 1997-5-1

[5]
Separable nanocomposite hydrogel microneedles for intradermal and sustained delivery of antigens to enhance adaptive immune responses.

Acta Biomater. 2024-9-1

[6]
Allogeneic GM-CSF-secreting tumor cell immunotherapies generate potent anti-tumor responses comparable to autologous tumor cell immunotherapies.

Clin Immunol. 2009-11

[7]
Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine.

Gene Ther. 2002-10

[8]
Comparison of fusion protein and DC vaccine in inhibition of mouse B16F10 melanoma tumor.

Biomed Pharmacother. 2017-11-6

[9]
Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand.

Cancer Res. 2000-6-15

[10]
Granulocyte-macrophage colony-stimulating factor-based melanoma cell vaccines immunize syngeneic and allogeneic recipients via host dendritic cells.

J Immunol. 2003-11-15

引用本文的文献

[1]
Cryomicroneedle Arrays for Biotherapeutics Delivery.

Small Sci. 2025-6-8

[2]
Functionalized Polymeric Microneedles for Transdermal Delivery of Ovalbumin Protein Antigen.

Pharmaceutics. 2025-6-4

[3]
Clinical Translation Challenges and Strategies for Tumour Vaccines Considering Multiple Delivery Routes.

Vaccines (Basel). 2025-4-27

[4]
Beyond the Needle: Innovative Microneedle-Based Transdermal Vaccination.

Medicines (Basel). 2025-2-7

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