Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity

IF 7 2区医学 Q1 DERMATOLOGY

Journal of Investigative Dermatology Pub Date : 2026-10-01 Epub Date: 2026-04-07 DOI:10.1016/j.jid.2026.03.026

Klara Klein, Litty Johnson, Ramona Rîca, Mirza Sarcevic, Gabriele Carta, Saskia Seiser, Adelheid Elbe-Bürger, Freyja Langer, Nowras Rahhal, Christoph Rademacher, Robert Wawrzinek, Federica Quattrone, Florian Sparber

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引用次数: 0

Abstract

Despite the success of mRNA therapeutics, challenges remain in optimizing immune responses and minimizing side effects. Cell-specific antigen delivery may help reduce required doses and improve vaccine efficacy. In this study, we report on a targeted delivery system for mRNA to a specific subset of skin-resident antigen-presenting cells: Langerhans cells. By functionalizing lipid nanoparticles with a langerin-specific glycomimetic ligand, we achieve selective mRNA delivery to both murine and human primary Langerhans cells with minimal off-target uptake, at the same time resulting in significantly increased mRNA translation. This targeted mRNA delivery not only enhances antigen presentation and T-cell responses but also enables dose-sparing and superior antitumor immunity compared with conventional immunization in a B16-OVA tumor model. Importantly, our platform’s high compatibility with various lipid nanoparticle formulations offers a flexible and precise tool for skin-directed mRNA delivery.

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朗格汉斯细胞靶向mRNA递送：一种剂量节约和增强抗肿瘤免疫的策略。

尽管mRNA疗法取得了成功，但在优化免疫反应和减少副作用方面仍然存在挑战。细胞特异性抗原递送可能有助于减少所需剂量并提高疫苗效力。在这项研究中，我们报道了mRNA的靶向递送系统到皮肤驻留抗原呈递细胞的特定子集-朗格汉斯细胞。通过将脂质纳米颗粒（LNPs）功能化，我们实现了对小鼠和人类原代朗格汉斯细胞的mRNA选择性递送，同时实现了最小的脱靶摄取，同时显著增加了mRNA的翻译。在B16-OVA肿瘤模型中，这种靶向mRNA递送不仅增强了抗原呈递和T细胞应答，而且与常规免疫相比，还实现了剂量节约和优越的抗肿瘤免疫。重要的是，我们的平台与各种脂质纳米颗粒配方的高兼容性为皮肤定向mRNA递送提供了灵活而精确的工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Investigative Dermatology 医学-皮肤病学

CiteScore

8.70

自引率

4.60%

发文量

1610

审稿时长

2 months

期刊介绍： Journal of Investigative Dermatology (JID) publishes reports describing original research on all aspects of cutaneous biology and skin disease. Topics include biochemistry, biophysics, carcinogenesis, cell regulation, clinical research, development, embryology, epidemiology and other population-based research, extracellular matrix, genetics, immunology, melanocyte biology, microbiology, molecular and cell biology, pathology, percutaneous absorption, pharmacology, photobiology, physiology, skin structure, and wound healing