Title |
Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial
|
---|---|
Published in |
Journal of Translational Medicine, March 2005
|
DOI | 10.1186/1479-5876-3-10 |
Pubmed ID | |
Authors |
Bernard Escudier, Thierry Dorval, Nathalie Chaput, Fabrice André, Marie-Pierre Caby, Sophie Novault, Caroline Flament, Christophe Leboulaire, Christophe Borg, Sebastian Amigorena, Catherine Boccaccio, Christian Bonnerot, Olivier Dhellin, Mojgan Movassagh, Sophie Piperno, Caroline Robert, Vincent Serra, Nancy Valente, Jean-Bernard Le Pecq, Alain Spatz, Olivier Lantz, Thomas Tursz, Eric Angevin, Laurence Zitvogel |
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 x 1014 molecules) or peptides (10 versus 100 mug/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 x 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 67% |
Australia | 1 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Portugal | 1 | <1% |
Germany | 1 | <1% |
Chile | 1 | <1% |
New Zealand | 1 | <1% |
Mexico | 1 | <1% |
Argentina | 1 | <1% |
Belgium | 1 | <1% |
Denmark | 1 | <1% |
China | 1 | <1% |
Other | 1 | <1% |
Unknown | 618 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 132 | 21% |
Researcher | 95 | 15% |
Student > Master | 82 | 13% |
Student > Bachelor | 74 | 12% |
Student > Doctoral Student | 30 | 5% |
Other | 84 | 13% |
Unknown | 131 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 148 | 24% |
Agricultural and Biological Sciences | 126 | 20% |
Medicine and Dentistry | 68 | 11% |
Immunology and Microbiology | 32 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 30 | 5% |
Other | 72 | 11% |
Unknown | 152 | 24% |