Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Exp Dermatol. 2021 Sep;30(9):1279-1289. doi: 10.1111/exd.14346. Epub 2021 May 3.
Dendritic cells (DC) are promising targets for immunotherapy of cancer. Clinically, immunization against cancer antigens by means of the most potent antigen-presenting cells, that is DC, remains an important treatment option in combination with the modern immune checkpoint approaches. Instead of adoptively transferring in vitro monocyte-derived DC, they can also be loaded in situ by antibody-mediated targeting of antigen. Conventionally, these vaccines are delivered by classical intradermal injections. Here, we tested an alternative approach, namely laser-assisted epicutaneous immunization. With an infrared laser ("Precise Laser Epidermal System"/P.L.E.A.S.E. Laser System), we created micropores in human skin and applied monoclonal antibodies (mAbs) against C-type lectins, for example DEC-205/CD205 and Langerin/CD207. Optimal parameters for formation of pores in epidermis and dermis were determined. We could induce pores of defined depths without enhanced apoptosis around them. Antibodies applied epicutaneously to the laser-porated skin could be detected both in Langerhans cells (LC) in situ in the epidermis and in migratory skin DC subsets from short term human skin explant culture, demonstrating uptake and transport of Langerin and DEC-205 mAbs. Efficacy of targeting was similar between the different laser treatments and pore depths. Thus, laser-assisted epicutaneous immunization may be a valuable alternative to intradermal injection, yet the loading efficacy of DC needs to be further improved.
树突状细胞（DC）是癌症免疫治疗的有前途的靶点。临床上，通过最有效的抗原呈递细胞（即 DC）对癌症抗原进行免疫接种仍然是与现代免疫检查点方法相结合的重要治疗选择。除了过继转移体外单核细胞衍生的 DC 外，还可以通过抗体介导的抗原靶向原位加载。传统上，这些疫苗通过经典的皮内注射给药。在这里，我们测试了一种替代方法，即激光辅助经皮免疫。我们使用红外激光（“精密激光表皮系统”/P.L.E.A.S.E.激光系统）在人体皮肤中创建微孔，并应用针对 C 型凝集素的单克隆抗体（mAb），例如 DEC-205/CD205 和 Langerin/CD207。确定了在表皮和真皮中形成孔的最佳参数。我们可以在不增加周围细胞凋亡的情况下诱导具有定义深度的孔。应用于激光穿孔皮肤的抗体可在表皮中的原位朗格汉斯细胞（LC）和短期人皮肤外植体培养中的迁移性皮肤 DC 亚群中检测到，表明 Langerin 和 DEC-205 mAb 的摄取和转运。不同激光处理和孔深度之间的靶向效率相似。因此，激光辅助经皮免疫可能是皮内注射的有价值替代方法，但 DC 的负载效率需要进一步提高。
