Chaput Nathalie, Taïeb Julien, Schartz Noël, Flament Caroline, Novault Sophie, André Fabrice, Zitvogel Laurence
ERIT-M 02-08 INSERM, Unité d'Immunologie, Département de Biologie Clinique, (+12), Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.
Blood Cells Mol Dis. 2005 Sep-Oct;35(2):111-5. doi: 10.1016/j.bcmd.2005.05.009.
Dendritic-cell-derived exosomes (DEX) secreted after dendritic cell loading with tumor peptides were found to mediate tumor rejection in mice. This observation prompted us to demonstrate that MHC class I/peptide complexes harbored onto exosomal membranes were capable of priming cytotoxic T cells and to mediate rejection of tumors expressing the relevant antigens. Moreover, DEX also promote NK cell activation in immunocompetent mice and NK cell-dependent antitumor effects. The first Phase I trial using DEX to immunize melanoma patients revealed the feasibility of DEX production in stage IV melanoma, their safety in long-term follow up and their bioactivity in vivo.
在用肿瘤肽负载树突状细胞后分泌的树突状细胞来源的外泌体（DEX）被发现可介导小鼠体内的肿瘤排斥反应。这一观察结果促使我们证明，外泌体膜上携带的MHC I类/肽复合物能够启动细胞毒性T细胞并介导表达相关抗原的肿瘤的排斥反应。此外，DEX还能促进免疫活性小鼠体内的NK细胞活化以及NK细胞依赖性抗肿瘤作用。第一项使用DEX免疫黑色素瘤患者的I期试验揭示了在IV期黑色素瘤中生产DEX的可行性、其长期随访的安全性以及其在体内的生物活性。
