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A human tumor model for preclinical immunotherapy trials



Geiger R.


External participants

Themeli Maria

(Third-party co-responsible)


To develop new anti-cancer immunotherapies, models that recapitulate the tumor microenvironment (TME) are essential. To date, tumor mouse models are used for such studies. However, ethical concerns regarding the use of laboratory animals along with poor translation to clinical settings in humans highlight their major shortcomings. Therefore, it is crucial to develop human TME model systems, which potentially predict the therapeutic efficacy of new treatments more accurately.

In this project, we aim at establishing a 3D TME-on-a-chip model that recapitulates key steps in the anti-tumor immune response. Immunogenic tumor spheroids will be exposed to dendritic cells, which then migrate to lymph-endothelial structures where they activate T cells. Activated T cells then traffic through endothelial structures and infiltrate and kill tumor spheroids. To generate sufficient amounts of HLA-matched immune cells, we will leverage induced pluripotent stem cells (iPSCs) and differentiate them into isogenic T cells and dendritic cells (DCs). Since iPSCs are self-renewing and pluripotent, they represent an unlimited source that can be differentiated into different immune cell types required for the human TME model.

We expect that this collaborative project will result in a standardized human 3D model system using engineerable and well-defined cell lines and iPSC-derived immune cells. After the model is established, we will partner with industry to develop a “TME-on-a-chip” kit that will be commercially available. We will extensively benchmark the model by applying available immunotherapeutics and compare the outcome to clinical data. A standardized, benchmarked and easily accessible human TME model may well become a viable alternative to mouse models.

Additional information

Start date
End date
48 Months
Funding sources
Swiss National Science Foundation / NRP - National Research Programmes / NRP 79