Induction of therapeutically relevant cytotoxic T lymphocytes in humans by percutaneous peptide immunization
Induction of therapeutically relevant cytotoxic T lymphocytes in humans by percutaneous peptide immunization
复制标题
DOI：
10.1158/0008-5472.can-06-1029
复制
发表时间：
2006-10-15
期刊：
影响因子：
11.2
通讯作者：
Seo, Naohiro
中科院分区：
文献类型：
--
作者：
Yagi, Hiroaki;Hashizume, Hideo;Seo, Naohiro
经皮肽免疫（PPI）是一种简单、无创的免疫方法，通过去除角质层的皮肤递送肽来诱导有效的CTL应答。在人类皮肤中这样的屏障破坏后，发现表皮朗格汉斯细胞虽然通过HLA表达和共刺激分子的上调而功能成熟，但迁移时树突数量减少。与MHC-肽四聚体/五聚体结合并产生IFN-γ的CD 8（+）群体在使用HLA I类限制性抗原肽的PPI后出现在血液中。PPI与黑色素瘤相关肽减少了病变大小，并抑制了7例晚期黑色素瘤患者中的4例肿瘤的进一步发展。这些有益作用伴随着具有体外细胞溶解活性的循环CTL的产生以及四聚体/五聚体结合细胞向消退病变中的广泛浸润。PPI在黑色素瘤患者中既不引起局部毒性，也不引起全身毒性或自身免疫性，但白癜风除外。因此，PPI代表了临床环境中癌症的新型治疗干预。
Percutaneous peptide immunization (PPI) is a simple and noninvasive immunization approach to induce potent CTL responses by peptide delivery via skin with the stratum corneum removed. After such a barrier disruption in human skin, epidermal Langerhans cells, although functionally matured through the up-regulation of HLA expression and costimulatory molecules, were found to emigrate with a reduced number of dendrites. CD8(+) populations binding to MHC-peptide tetramers/pentamers and producing IFN-gamma appeared in the blood after PPI with HLA class I-restricted antigenic peptides. PPI with melanoma-associated peptides reduced the lesion size and suppressed further development of tumors in four of seven patients with advanced melanoma. These beneficial effects were accompanied by the generation of circulating CTLs with in vitro cytolytic activity and extensive infiltration of tetramer/pentamer-binding cells into regressing lesions. PPI elicited neither local nor systemic toxicity or autoimmunity, except for vitiligo, in patients with melanoma. Therefore, PPI represents a novel therapeutic intervention for cancer in the clinical setting.