Targeted eradication of cancer stem cells by chimeric T cell receptors.
Immunology
Final Report Abstract
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 report an immunotherapeutic approach of targeting the minor CSC subfraction by exploiting the stem cell related wnt-pathway is described. It was 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, the 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 the mouse model system. These findings implicate a leading role for immunotherapy when targeting the tumor stem cell fraction.
