Establishment of 2D and 3D Primary Cell Cultures From Gastric and Gastroesophageal Junction Cancer

Gastric cancer is among the leading causes of cancer-related death worldwide. Surgery or radiation monotherapy are applicable as treatment for localized tumors, however, the majority of patients are diagnosed in an advanced disease state requiring systemic therapy Chemotherapies are non-specific, affecting healthy tissues, and the overall response rate in gastric tumors is limited. As such, there is a large unmet medical need for targeted therapies against gastric tumors. Recent advances in the field of onco-immunology unraveled the mechanisms of immune response against cancer, leading to the development of immunotherapeutic strategies such as: immune check point inhibitors (ICIs), and advanced therapy medicinal products (ATMPs), e.g. chimeric antigen receptor (CAR) T cells. ICIs and CAR T cell therapy in particular have evolved as novel therapeutic cornerstones against hematological disease, but their efficacy against solid tumors remains poor. Accordingly, a minority of gastric cancer patients show durable responses to immunotherapies and there is currently no cellular immunotherapy available for gastric cancer. Further, gastric tumors are heterogeneous due to genomic changes, cellular composition, and the microenvironment, conferring a very variable response to immunotherapies. Thus, a personalized approach is needed, in order to understand individual resistance mechanisms and to predict which patients are most suitable for which therapy.

To address this need, test systems resembling patient-specific tumor biology are required. Cell lines lack 3D context and lose their genetic fidelity through passaging. Patient-derived murine xenograft models provide 3D environment and multi-organ context, but the xeno-environment hampers reliability and translatability. The investigators envision patient-derived tumor organoids as a superior model, as they are 3D self-organizing structures which reflect the tumor complexity. In addition, they have the potential to serve as patient avatars and preclinical models to predict the efficacy of therapies.

In this study, the investigators will establish patient-derived organoids and to study individual tumor biology and as testing platforms for (immune-) therapies. The investigators further investigate the individual biology of the patients tumors and healthy tissues to not only understand the heterogeneous mechanisms of gastric cancer but also the heterogeneous mechanisms of healthy gastric tissue in the fields of infectiology and immunology.