Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Dijkstra, Krijn K., Cattaneo, Chiara M., Weeber, Fleur, Chalabi, Myriam, van de Haar, Joris, Fanchi, Lorenzo F., Slagter, Maarten, van der Velden, Daphne L., Kaing, Sovann, Kelderman, Sander, van Rooij, Nienke, van Leerdam, Monique E., Depla, Annekatrien, Smit, Egbert F., Hartemink, Koen J., de Groot, Rosa, Wolkers, Monika C., Sachs, Norman, Snaebjornsson, Petur, Monkhorst, Kim, Haanen, John, Clevers, Hans, Schumacher, Ton N. & Voest, Emile E.

Published: 06/09/2018

Summary Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.

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