Anti-cancer therapy using dendritic cells and apoptotic tumour cells: preclinical data in human mesothelioma and acute myeloid leukemia
Abstrakt
We have recently reported in an experimental model, that treatments based on the injections of dendritic cells which had phagocytosed apoptotic bodies derived from tumour cells were particularly effective in the cure of tumour-bearing animals. We proposed that systems using, processing and presentation of antigenic molecules from antigen-presenting cells primed with apoptotic bodies can offer new opportunities in anti-cancer treatment.
We first established the technical conditions for purification, characterisation and production of tumour cells isolated from fresh pleural liquid or blood. Then we compared efficacy of different apoptotic inducers agents on the cancer cells in culture.
The apoptotic tumour cells were purified, characterised and maintained in coculture with monocytes-derived immature dendritic cells. We subsequently investigated the effect of the maturation process on phagocytosis of apoptotic bodies.
We have shown that whatever the nature of the apoptotic cells they are phagocytosed by the dendritic cells which were efficiently matured using the combination of TNFalpha + Poly I:C. Furthermore, we demonstrated that the generation of the mature dendritic cells pulsed with apoptotic tumour cells, successfully generated CD4(+) (Th1) and CD8(+) (CTL) cells.
All the experimental procedures that we have used were developed with clinical use in mind, using Good Manufacturing Products. We are presently investigating the feasibility of such a "vaccine" for the treatment of asbestos mesothelioma or acute myeloid leukaemia.