Alpha particles and induction of an anti-tumour immune response

Abstract

OBJECTIVES: Radioimmunotherapy (RIT) is an approach allowing targeting of radioelements to tumours, usually through the use of antibodies specific for tumour antigens. The radiations emitted by the radioelements then induce direct killing of the targeted cells as well as indirect killing through bystander effect. Interestingly, it has been shown that ionizing radiations, in some settings of external radiotherapy, can foster an immune response directed against tumour cells. Our research team is dedicated to the development of alpha RIT, i. e RIT using alpha particle emitters, we therefore decided to study the effects of such particles on tumour cells in regards to their immunogenicity. Material&METHODS: We studied the effects of bismuth-213, an alpha emitter, on cellular death and autophagy in a mouse (5T33) and a human (LP-1) myeloma cell line. Using flow cytometry analysis, we measured the expression of MHC molecules and several DAMPs at the cell surface to determine whether irradiation with bismuth-213 could cause the tumour cells to be recognized by the immune system. We also tested the irradiated cells’ culture media by ELISA to check whether DAMPs were secreted after treatment with bismuth-213. Finally, a co-culture of dendritic cells with irradiated tumour cells or their culture media was performed to test whether it would induce dendritic cell activation. Results: Only slight levels of apoptosis and necrosis were detected within the 48 hours following irradiation in the studied cell lines, however they both exhibited signs of autophagy. No increase in membrane or extracellular expression of DAMPs was observed after treatment with bismuth-213, or in the expression of MHC class I and II. However, the co-culture experiments indicated that soluble factors are released in the culture media after irradiation with bismuth-213, which are able to induce dendritic cell activation. Conclusion: These preliminary data suggest that alpha particles could be of interest in rising an immune response associated to RIT.JRC.E.5-Nuclear chemistr