Tumor infiltrating HLA-matched CD4+ T cells retargeted against Hodgkin and Reed-Sternberg cells

Hodgkin's lymphoma (HL) is one of the most frequent hematological malignancies. Due to its extraordinary composition, few tumor cells surrounded by a reactive infiltrate, HL can be seen as an ideal model system for research focusing on tumor immunology. In fact, the tumor cells of HL, so called Hodgkin/Reed-Sternberg (HRS) cells attract CD4+ T cells, which then build rosettes with the HRS cells. HRS cells further modulate the tumor microenvironment with the help of CD4+ T cells to avoid tumor rejection. Here, we mimicked this scenario using compatible CD4+ T cells receiveing data of profound interactions for the first time, as former studies were performed with allogeneic donors. Finally, we genetically retargeted compatible CD4+ T cells to kill HRS cells.

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Rengstl B, Schmid F, Weiser C, Döring C, Heinrich T, Warner K, Becker PS, Wistinghausen R, Kameh-Var S, Werling E, Billmeier A, Seidl C, Hartmann S, Abken H, Küppers R, Hansmann ML, Newrzela S