DC-TARGETED VECTOR · Development of dendritic cell-targeted lentivirus vectors for vaccination
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-09-01 → 2007-08-31
- EU contribution
- €168,798
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - DC-TARGETED VECTOR (Development of dendritic cell-targeted lentivirus vectors for vaccination)
The objective of this project was to specifically modify dendritic cells using lentivectors to fight against cancer and infectious diseases. Dendritic cells are key controllers of the immune system. They either start the fighting against cancer and pathogens like bacteria and viruses, or they suppress the response against harmless antigens such as polen or commensal bacteria. In the case of cancer, dendritic cells have to be stimulated to allow the immune system to destroy cancer cells. We have achieved this by including therapeutic genes inside the cells that activate them to direct an immune response against cancer. In the case of allergic diseases, dendritic cells have to be de-activated. We have also achieved dendritic cell deactivation by modifying signals inside the cells. Summarising, we have developed a successful approach to control dendritic cells to manipulate the immune system, either activating it to fight against cancer, or deactivating it to prevent allergy and autoimmune diseases.
Data: CORDIS, © European Union
Project objective
Dendritic cells (DCs) are one of the key antigen presenting cells from the immune system to mount effective immune responses against pathogens and tumours. Several approaches for clinical trials involving this cell type are currently under study, including cellular vaccination using DCs loaded with both pathogen and tumour antigens.However, these procedures, although providing promising results, are nowadays expensive and difficult to standarized. Therefore, this project will employ a rational design approach to the development of new vaccine vectors, by engineering lentivirus vectors specifically targeted to dendritic cells (DCs).For this purpose, single chain antibodies (scFvs) specific for dendritic cells will be constructed from a phage display library. DC-specific scFvs will be fused to the MLV-A envelope protein through a blocking peptide followed by a matrix metalloprotease (MMP) recognition sequence. Lentivirus vectors based on defective HIV-1 genomes will be produced from stable packaging cell lines expressing DC-targeted chimeric scFv-MLV envelopes.Transduction specificity and efficiency will be assayed both in cell cultures and in vivo. Antigens of interests will be expressed alone or co-expressed with DC-activating molecules, and immune responses against these antigens will be measured.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE OF LONDON · LONDONCoordinatorCity levelUnited Kingdom
Links
Data: CORDIS, © European Union