Evaluation of the therapeutic potential of the alpha radioimmunotherapy in combination with the adoptive transfer of tumor-specific T cells

Alpha radioimmunotherapy (α-RIT) is a targeted anti-cancer therapy which uses a vector (in general a monoclonal antibody) recognizing an antigen expressed on the surface of tumor cells. This technique allows to vectorize α particle emitters on tumor sites in order to specifically destroy cancer cells. α-emitters, such as bismuth-213, represent an ideal tool for the destruction of isolated or small clusters of tumor cells. We have shown in a murine adenocarcinoma model that α irradiation can initiate an effective immune dependent antitumor T cell response. These results demonstrated that the immune system can be stimulated after α irradiation, suggesting the possibility of combining α-RIT with immunotherapy strategies such as the transfer of tumor-specific T-lymphocytes. Here, we demonstrate the efficacy of the combination therapy in a murine model of multiple myeloma in syngeneic immunocompetent mice. The success in the treatment of this disseminated disease demonstrates the potentiation of the injected T-lymphocytes effectiveness after α-RIT and indicates that the immune system is stimulated. These results suggest that the two treatments work synergistically for tumor destruction and for the establishment of an immune environment, which leads to the elimination of multiple myeloma in our model. This preclinical study highlights the feasibility and relevance of combining these two strategies and thus opens the possibility for its clinical application. (author)