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Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells
Authors:Diana Lindner  Claudia Arndt  Liliana Rodrigues Loureiro  Anja Feldmann  Alexandra Kegler  Stefanie Koristka  Nicole Berndt  Nicola Mitwasi  Ralf Bergmann  Marcus Frenz  Michael P. Bachmann
Abstract:Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-γ and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells.
Keywords:prostate stem cell antigen   prostate cancer   radiation   immunotherapy   bispecific T cell engager
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