Frankenburg Shoshana, Grinberg Igor, Bazak Ziva, Fingerut Lena, Pitcovski Jacob, Gorodetsky Raphael, Peretz Tamar, Spira Ram M, Skornik Yehuda, Goldstein Ronald S
Sharett Institute of Oncology, Hadassah Medical Organization, POB 12000, Jerusalem 91120, Israel.
Vaccine. 2007 Jun 6;25(23):4564-70. doi: 10.1016/j.vaccine.2007.04.025. Epub 2007 Apr 25.
Transcutaneous immunization aims at taking advantage of the skin's immune system for the purpose of immunoprotection. In the present study, we evaluated the potential of topical delivery of a recombinant melanoma protein, HR-gp100, derived from a shortened sequence of the native gp100 gene. The protein was applied on the skin, with and without the addition of two forms of heat labile enterotoxin (nLT and LTB). HR-gp100 fused to Haptide, a cell penetrating 20mer peptide (HR-gp100H) was also tested. Topical HR-gp100 and HR-gp100H application on the ears of mice elicited the production of specific antibodies, and transcutaneous delivery to intact human skin induced dose-dependent LC activation. nLT and LTB also activated LC, but did not further increase the activation induced by HR-gp100. These results show that HR-gp100, an antigenic tumor-derived protein, activates the immune system following transcutaneous delivery, as shown by both Langerhans cell activation and induction of antibody production.
经皮免疫旨在利用皮肤的免疫系统实现免疫保护。在本研究中,我们评估了局部递送源自天然gp100基因缩短序列的重组黑色素瘤蛋白HR-gp100的潜力。该蛋白被应用于皮肤,添加和不添加两种形式的热不稳定肠毒素(nLT和LTB)。还测试了与Haptide(一种细胞穿透性20聚体肽)融合的HR-gp100(HR-gp100H)。在小鼠耳部局部应用HR-gp100和HR-gp100H可引发特异性抗体的产生,经皮递送至完整的人体皮肤可诱导剂量依赖性的朗格汉斯细胞(LC)活化。nLT和LTB也可激活LC,但不会进一步增加HR-gp100诱导的活化。这些结果表明,抗原性肿瘤衍生蛋白HR-gp100在经皮递送后可激活免疫系统,这通过朗格汉斯细胞活化和抗体产生的诱导得以体现。