Development of universal vaccinal dendritic cells lines for cancer treatment
The development of efficient vaccines for the treatment of cancers is a major public health issue but remains a challenge. The induction of cytotoxic specific T cell able to recognize and lyse malignant cells is the main goal of i...
The development of efficient vaccines for the treatment of cancers is a major public health issue but remains a challenge. The induction of cytotoxic specific T cell able to recognize and lyse malignant cells is the main goal of immunotherapeutic strategies based on dendritic cells. The fellow has developed a unique cell line (GEN2.2) from the new Plasmacytoid Dendritic Cell (PDC) type. He demonstrated its tremendous potential in allogeneic setting to induce the activation and proliferation of specific efficient cytotoxic T lymphocytes in vitro (melanoma patients’ samples) and in vivo (preclinical humanized mouse model). Allogeneic PDCs therefore represents a new promising immunotherapeutic strategy to fight cancer. The project aims to create a set of universal off-the-shelf dendritic cell lines based on GEN2.2. The current strategy is based on irradiated GEN2.2 loaded with immunogenic peptides derived from tumor antigen presented by HLA-A*0201 allele. This strategy, however, is limited to the patients with the corresponding HLA allele and to the known peptides chemically synthesized. In collaboration with the University College London, the fellow proposes to improve this vaccine strategy by engineering genetically modified cell lines, either coding for i) the antigenic peptide to avoid the loading step, ii) the antigens as the whole protein to enlarge the spectrum of presented peptides, or iii) other HLA class I antigens to target a larger number of patients. This project is ambitious and in the scope of the developments in the immunotherapeutic field. It proposes to enlarge the patient population and the cancers for which this new and promising strategy could be used. The Marie Curie Action proposed here is an adequate opportunity for the fellow to overcome his weaknesses (genetic engineering, English language) and increase his international renown to develop his projects involving genetic aspects and to gain leadership skills for managing European projects.ver más
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