Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Cancer Res. 2013 Feb 1;73(3):1063-75. doi: 10.1158/0008-5472.CAN-12-2583. Epub 2013 Jan 23.
Vaccination against cancer by using dendritic cells has for more than a decade been based on dendritic cells generated ex vivo from monocytes or CD34(+) progenitors. Here, we report on the first clinical study of therapeutic vaccination against cancer using naturally occurring plasmacytoid dendritic cells (pDC). Fifteen patients with metastatic melanoma received intranodal injections of pDCs activated and loaded with tumor antigen-associated peptides ex vivo. In vivo imaging showed that administered pDCs migrated and distributed over multiple lymph nodes. Several patients mounted antivaccine CD4(+) and CD8(+) T-cell responses. Despite the limited number of administered pDCs, an IFN signature was observed after each vaccination. These results indicate that vaccination with naturally occurring pDC is feasible with minimal toxicity and that in patients with metastatic melanoma, it induces favorable immune responses.
十多年来,利用树突状细胞进行癌症疫苗接种一直基于从单核细胞或 CD34(+)祖细胞体外生成的树突状细胞。在这里,我们报告了首例使用天然浆细胞样树突状细胞(pDC)进行癌症治疗性疫苗接种的临床研究。15 名转移性黑色素瘤患者接受了淋巴结内注射经体外激活和加载肿瘤抗原相关肽的 pDC。体内成像显示,给予的 pDC 迁移并分布于多个淋巴结中。一些患者产生了抗疫苗 CD4(+)和 CD8(+)T 细胞反应。尽管给予的 pDC 数量有限,但每次接种后都观察到 IFN 特征。这些结果表明,用天然存在的 pDC 进行疫苗接种是可行的,且毒性最小,在转移性黑色素瘤患者中,它可诱导有利的免疫反应。