Final Report Summary - PDCTHERAPY (Development of universal vaccinal dendritic cells lines for cancer treatment)
Project context and objectives
The development of efficient vaccines for the treatment of cancers represents a major public health issue but remains a challenge. Given the fact that cytotoxic T lymphocytes (CTL) are able to recognise and lyse malignant cells, many therapeutic trials have been designed to take advantage of their response, although the overall objective response rate for all vaccine treatments is low (less than 5 %). Therefore, there is a strong need for novel, off-the-shelf immunotherapeutic strategies to overcome limitations of current protocols. Before starting the project, a new PDC-based immunotherapy had been investigated in human anti-tumour treatment. The strategy, called 'GENiusVac', consists of loading an irradiated PDC cell line (GEN) with peptides of interest to induce HLA-A*0201-restricted antigen-specific CTL from allogeneic HLA-A*0201-matched leucocytes (Aspord et al. 2010, Aspord et al. 2011). The proof of concept has been brought in vitro and in vivo with cells from healthy donors and patients with a melanoma.
So, the efficiency and design of the immunotherapeutic approach render the GENiusVac strategy very attractive for further clinical developments. However, this strategy has a few drawbacks.
Project results
The PDCTHERAPY project has allowed an engineering strategy to be validated to create universal "off-the-shelf" antigen-presenting cell lines. Some aspects have still to be validated but the results obtained so far are particularly encouraging. As the cell line will be ready in a few months for clinical applications, the very interesting work done during this project will constitute a new generation of PDC-based immunostrategy for the majority of the European population for a wide range of cancers. Moreover, it has already brought new lines of research for the European Union and will allow the setting up of a clinical trial in numerous countries within the EU which are already involved in such cell therapy.
The Marie Curie Action was a very good opportunity for Joël Plumas to overcome his weaknesses and increase his international renown, to continue to develop his projects involving genetic aspects, to gain leadership skills for managing European projects, and to become a leader in the European scientific community. Finally, Joël Plumas, with his expertise in PDC, and Martin Pule, with his expertise in genetic engineering of immunotherapeutic cells, have brought a complementary dimension to this ambitious project to make a truly universal off-the-shelf dendritic cell-line-based vaccine, something which could not be achieved by both investigators working alone. They will remain in close contact to pursue the project in London and in Grenoble.
The development of efficient vaccines for the treatment of cancers represents a major public health issue but remains a challenge. Given the fact that cytotoxic T lymphocytes (CTL) are able to recognise and lyse malignant cells, many therapeutic trials have been designed to take advantage of their response, although the overall objective response rate for all vaccine treatments is low (less than 5 %). Therefore, there is a strong need for novel, off-the-shelf immunotherapeutic strategies to overcome limitations of current protocols. Before starting the project, a new PDC-based immunotherapy had been investigated in human anti-tumour treatment. The strategy, called 'GENiusVac', consists of loading an irradiated PDC cell line (GEN) with peptides of interest to induce HLA-A*0201-restricted antigen-specific CTL from allogeneic HLA-A*0201-matched leucocytes (Aspord et al. 2010, Aspord et al. 2011). The proof of concept has been brought in vitro and in vivo with cells from healthy donors and patients with a melanoma.
So, the efficiency and design of the immunotherapeutic approach render the GENiusVac strategy very attractive for further clinical developments. However, this strategy has a few drawbacks.
Project results
The PDCTHERAPY project has allowed an engineering strategy to be validated to create universal "off-the-shelf" antigen-presenting cell lines. Some aspects have still to be validated but the results obtained so far are particularly encouraging. As the cell line will be ready in a few months for clinical applications, the very interesting work done during this project will constitute a new generation of PDC-based immunostrategy for the majority of the European population for a wide range of cancers. Moreover, it has already brought new lines of research for the European Union and will allow the setting up of a clinical trial in numerous countries within the EU which are already involved in such cell therapy.
The Marie Curie Action was a very good opportunity for Joël Plumas to overcome his weaknesses and increase his international renown, to continue to develop his projects involving genetic aspects, to gain leadership skills for managing European projects, and to become a leader in the European scientific community. Finally, Joël Plumas, with his expertise in PDC, and Martin Pule, with his expertise in genetic engineering of immunotherapeutic cells, have brought a complementary dimension to this ambitious project to make a truly universal off-the-shelf dendritic cell-line-based vaccine, something which could not be achieved by both investigators working alone. They will remain in close contact to pursue the project in London and in Grenoble.