A three-dimensional ex vivo platform for assessing targeted immunotherapeutic agents
Francesca Chiavarro1, Tamara Tanos1, Irina Agarkova1, Lei He2, Jens Kelm1, Patrick Guye1, Sumeer Dhar1
1InSphero AG, Wagistrasse 27, Schlieren, 8952, Switzerland
2InSphero Inc, TechPlace, 74 Orion Street, Brunswick, ME 04011
Multicellular tumor spheroid (MCTS)-based 3D ex vivo platforms are extensively used to evaluate the activity of cytotoxic drugs, targeted molecules, and antibodies. To increase the translational value of this model, it is of great importance to maintain tumor microenvironment-like conditions (immune and other stromal cells). We have established a 96 well based 3D ex vivo system using well known tumor cell lines derived from non-small cell lung cancer and breast cancer expressing wide range of PDL1 levels. The cells were cultured with stromal and immune cells to replicate tumor-like microenvironment. Upon treatment with CD3/CD28 stimulated PBMCs, efficient infiltration of immune cells was observed using an immunohistochemical approach. Subsequently, these MCTS were exposed to known PD1 inhibitors, resulting in an increased elimination of target cells within the MCTS.
We are now working on expanding our immune-competent 3D models by screening multiple tumor cell lines and supplementing the microtumors with activated effector cells, in particular T and NK cells. This with an aim of investigating novel drug combination approaches and evaluating immunomodulatory therapies. In conclusion, this study demonstrates the power and versatility of our 3D MCTS platform for the assessment of antibody-based targeted tumor cell elimination.