D'Amico Carmine, Fusciello Manlio, Hamdan Firas, D'Alessio Federica, Bottega Paolo, Saklauskaite Milda, Russo Salvatore, Cerioni Justin, Elbadri Khalil, Kemell Marianna, Hirvonen Jouni, Cerullo Vincenzo, Santos Hélder A
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
Department of Pharmaceutical Biosciences, University of Helsinki, Faculty of Pharmacy ImmunoViroTherapy Lab, Drug Research Program, Viikinkaari 5, E00790, Helsinki, Finland.
Bioact Mater. 2024 Nov 19;45:115-127. doi: 10.1016/j.bioactmat.2024.11.006. eCollection 2025 Mar.
Microneedles (MNs) are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation. This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses (PeptiCRAd), whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens. The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure, induction of immune response, and tumor eradication. The findings indicated that MN-delivered PeptiCRAd was effective in peptide presentation leading to complete tumor rejection when mice were pre-vaccinated. A rise in the cDC1 population in the lymph nodes of the MN treated mice led to an increase in the effector memory T cells in the body. Thus, the results of this study demonstrate that the combination of MN technology with PeptiCRAd may provide a safer, more tolerable, and efficient approach to cancer immunotherapy, potentially translatable to other therapeutic applications.
微针是癌症免疫治疗中的一种前瞻性系统,旨在克服抗原正确递送和呈递方面的障碍。本研究旨在确定微针递送肽包被的条件复制腺病毒(PeptiCRAd)的潜力,其中肽可增强呈递肿瘤相关抗原的腺病毒的免疫原性。测试了PeptiCRAd与含有聚乙烯吡咯烷酮和蔗糖的微针的组合在结构保存、免疫反应诱导和肿瘤根除方面的效果。研究结果表明,当小鼠预先接种疫苗时,微针递送的PeptiCRAd在肽呈递方面有效,可导致肿瘤完全消退。微针治疗小鼠淋巴结中cDC1细胞群的增加导致体内效应记忆T细胞增加。因此,本研究结果表明,微针技术与PeptiCRAd的组合可能为癌症免疫治疗提供一种更安全、更耐受且有效的方法,有可能转化为其他治疗应用。