Terán-Navarro Hector, Calderon-Gonzalez Ricardo, Salcines-Cuevas David, García Isabel, Marradi Marco, Freire Javier, Salmon Erwan, Portillo-Gonzalez Mar, Frande-Cabanes Elisabet, García-Castaño Almudena, Martinez-Callejo Virginia, Gomez-Roman Javier, Tobes Raquel, Rivera Fernando, Yañez-Diaz Sonsoles, Álvarez-Domínguez Carmen
Group of Listeria based Nanovaccines and cellular vaccines and their applications in biomedicine, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Cantabria, Spain.
Bionanoplasmonics Laboratory, CIC biomaGUNE and Biomedical Research Networking Center in Bioengineering, Nanomaterials and Nanomedicine (CIBER-BBN), Donostia-San Sebastián, Gipuzkoa, Spain.
Oncoimmunology. 2018 Nov 10;8(2):e1541534. doi: 10.1080/2162402X.2018.1541534. eCollection 2019.
Gold glyconanoparticles loaded with the listeriolysin O peptide 91-99 (GNP-LLO), a bacterial peptide with anti-metastatic properties, are vaccine delivery platforms facilitating immune cell targeting and increasing antigen loading. Here, we present proof of concept analyses for the consideration of GNP-LLO nanovaccines as a novel immunotherapy for cutaneous melanoma. Studies using mouse models of subcutaneous melanoma indicated that GNP-LLO nanovaccines recruite and modulate dendritic cell (DC) function within the tumour, alter tumour immunotolerance inducing melanoma-specific cytotoxic T cells, cause complete remission and improve survival. GNP-LLO nanovaccines showed superior tumour regression and survival benefits, when combined with anti-PD-1 or anti-CTLA-4 checkpoint inhibitors, resulting in an improvement in the efficacy of these immunotherapies. Studies on monocyte-derived DCs from patients with stage IA, IB or IIIB melanoma confirmed the ability of GNP-LLO nanovaccines to complement the action of checkpoint inhibitors, by not only reducing the expression of cell-death markers on DCs, but also potentiating DC antigen-presentation. We propose that GNP-LLO nanovaccines function as immune stimulators and immune effectors and serve as safe cancer therapies, alone or in combination with other immunotherapies.
负载李斯特菌溶血素O肽91 - 99（GNP - LLO）的金糖纳米颗粒是一种具有抗转移特性的细菌肽，是促进免疫细胞靶向和增加抗原负载的疫苗递送平台。在这里，我们提供概念验证分析，以考虑将GNP - LLO纳米疫苗作为皮肤黑色素瘤的一种新型免疫疗法。使用皮下黑色素瘤小鼠模型的研究表明，GNP - LLO纳米疫苗可募集并调节肿瘤内树突状细胞（DC）的功能，改变肿瘤免疫耐受性，诱导黑色素瘤特异性细胞毒性T细胞，实现完全缓解并提高生存率。当与抗PD - 1或抗CTLA - 4检查点抑制剂联合使用时，GNP - LLO纳米疫苗显示出卓越的肿瘤消退和生存益处，从而提高了这些免疫疗法的疗效。对IA期、IB期或IIIB期黑色素瘤患者单核细胞衍生的DC的研究证实，GNP - LLO纳米疫苗不仅能降低DC上细胞死亡标志物的表达，还能增强DC的抗原呈递能力，从而补充检查点抑制剂的作用。我们提出，GNP - LLO纳米疫苗可作为免疫刺激剂和免疫效应器，单独或与其他免疫疗法联合使用，是安全的癌症治疗方法。
