| Title: |
Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial |
| Authors: |
Piperno Sophie, Movassagh Mojgan, Dhellin Olivier, Bonnerot Christian, Boccaccio Catherine, Amigorena Sebastian, Borg Christophe, Leboulaire Christophe, Flament Caroline, Novault Sophie, Caby Marie-Pierre, André Fabrice, Chaput Nathalie, Dorval Thierry, Escudier Bernard, Robert Caroline, Serra Vincent, Valente Nancy, Le Pecq Jean-Bernard, Spatz Alain, Lantz Olivier, Tursz Thomas, Angevin Eric, Zitvogel Laurence |
| Source: |
Journal of Translational Medicine, Vol 3, Iss 1, p 10 (2005) |
| Publisher Information: |
BMC, 2005. |
| Publication Year: |
2005 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
exosomes, dendritic cells, phase I trial, cancer vaccine, immunotherapy, Medicine |
| More Details: |
Abstract Background DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. Patients and methods Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules) or peptides (10 versus 100 μg/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. Results The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. Conclusion The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1479-5876 |
| Relation: |
http://www.translational-medicine.com/content/3/1/10; https://doaj.org/toc/1479-5876 |
| DOI: |
10.1186/1479-5876-3-10 |
| Access URL: |
https://doaj.org/article/bb48888a48854a99987f803f60fd99d3 |
| Accession Number: |
edsdoj.bb48888a48854a99987f803f60fd99d3 |
| Database: |
Directory of Open Access Journals |
