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Project
The development of preclinical models to evaluate combinatorial strategies for augmenting the potency of dendritic cell-based immunotherapy (FWOAL640)
Melanoma is a highly malignant tumor, responsible for the majority of skin-cancer related deaths. Only complete surgical resection in an early stage can cure the disease. Once the cancer has spread beyond the limits for surgical resection, the chance of complete remission is small with the currently available therapies.
Two novel strategies are under development for the treatment of malignant melanoma: immunotherapy and molecular-targeted therapies. We have a long-standing expertise in the development of autologous vaccines based on dendritic cells (DCs). We are currently co-electroporating DCs with a TriMix of costimulatory molecules and a tumor associated antigen. We often observe antigen-specific T cell responses in vaccinated patients, but clinical responses remain low. This is probably due to the fact that the induced T cells are unable to break the established tumor tolerance. It is generally accepted that combining DC-based vaccination with molecular-targeted therapy might enable the induced T cells to mediate tumor rejection. It is not yet clear however how best to integrate these two modalities. We here want to develop novel models to investigate this, both using in vivo murine models and in vitro using human cells. Moreover, these models will allow us to better understand tumor-biology and -immunology.
Two novel strategies are under development for the treatment of malignant melanoma: immunotherapy and molecular-targeted therapies. We have a long-standing expertise in the development of autologous vaccines based on dendritic cells (DCs). We are currently co-electroporating DCs with a TriMix of costimulatory molecules and a tumor associated antigen. We often observe antigen-specific T cell responses in vaccinated patients, but clinical responses remain low. This is probably due to the fact that the induced T cells are unable to break the established tumor tolerance. It is generally accepted that combining DC-based vaccination with molecular-targeted therapy might enable the induced T cells to mediate tumor rejection. It is not yet clear however how best to integrate these two modalities. We here want to develop novel models to investigate this, both using in vivo murine models and in vitro using human cells. Moreover, these models will allow us to better understand tumor-biology and -immunology.
Date:1 Jan 2012 → 31 Dec 2015
Keywords:Stem Cell, Blood, Coagulation, Myeloma, Immunology, Microbiology, HLA, Hematology, Lymphoma, cancer, Bone Marrow Transplantation
Disciplines:Basic sciences, Biological sciences