The Cancer Stem Cell (CSC) hypothesis puts a, not necessarily rare, subpopulation of cells on the top of a tumor forming hierarchy, pointing to the importance of their destruction when aiming on a final cure. However, current studies targeting CSCs rather focus on the tumor initiating capacities of these cells than on their maintaining capacity in an established lesion. In this presentation we describe an immunotherapeutic approach of targeting the minor CSC subfraction by exploiting the stem cell related wnt-pathway. Within a fully syngeneic mouse tumor model, we labelled 4T1 breast tumor cells by lentiviral transduction to express a foreign antigen in wnt-active cells. When transferred into the host, these cells recapitulated CSC behavior and were concomitantly targetable by chimeric antigen receptor engineered T cells. All mice receiving a CSC specific CAR treatment showed long term metastases free survival, although a minority of cells served as actual aim of treatment. We investigated the consequences of CSC eradication at different time points after treatment and found that a memory effect, provided by engineered T cells, is essential to keep the re-formation of CSCs from bulk tumor cells under control. Furthermore, our treatment setting is able to re-activate the host's non engineered T cells against the majority of tumor cells, which leads to a long lasting tumor-free survival in our mouse model system. These findings implicate a leading role for immunotherapy when targeting the tumor stem cell fraction.
Citation Format: Patrick Schmidt, Nicolas Desbaillets, Pierre Dessen, Nancy Thompson, Joerg Huelsken, Dirk Jäger. Successful immunotherapy of cancer stem cells requires memory and the adaptive immune system of the host. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B067.
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