Title |
A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer
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Published in |
Journal of Translational Medicine, February 2005
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DOI | 10.1186/1479-5876-3-9 |
Pubmed ID | |
Authors |
Michael A Morse, Jennifer Garst, Takuya Osada, Shubi Khan, Amy Hobeika, Timothy M Clay, Nancy Valente, Revati Shreeniwas, Mary Ann Sutton, Alain Delcayre, Di-Hwei Hsu, Jean-Bernard Le Pecq, H Kim Lyerly |
Abstract |
BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1-2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 50% |
Australia | 1 | 25% |
Kenya | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | <1% |
Denmark | 2 | <1% |
Chile | 1 | <1% |
New Zealand | 1 | <1% |
Germany | 1 | <1% |
Argentina | 1 | <1% |
Portugal | 1 | <1% |
Iran, Islamic Republic of | 1 | <1% |
Belgium | 1 | <1% |
Other | 0 | 0% |
Unknown | 484 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 106 | 21% |
Researcher | 80 | 16% |
Student > Master | 62 | 13% |
Student > Bachelor | 59 | 12% |
Student > Doctoral Student | 22 | 4% |
Other | 63 | 13% |
Unknown | 103 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 112 | 23% |
Agricultural and Biological Sciences | 90 | 18% |
Medicine and Dentistry | 56 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 29 | 6% |
Immunology and Microbiology | 23 | 5% |
Other | 55 | 11% |
Unknown | 130 | 26% |