Abstract 240: Mix and match - A comprehensive pipeline for matched patient-derived PDX and PD3D® modelsfor cancer research and preclinical drug development

Abstract

Abstract Relevant in vivo and in vitro cancer models have been invaluable for our current understanding of cancer biology, as well as for therapy development. Using appropriate models in the drug development process significantly supports reliable and swift decision making in proceeding along the value chain. In parallel, animal experiments can be designed more specific to the scientific and regulatory needs, resulting in shorter development cycles and eventually the availability of better therapies for cancer patients. Patient-derived xenografts (PDX) are generated by implantation of cancerous tissue from a patient’s tumor either under the skin (ectopic) or into the organ of tumor origin (orthotopic) of an immunocompromised mouse and are the most used in vivo model for preclinical drug development. Patient-derived 3D cell culture models (PD3D®) are gaining increasing significance as relevant in vitro cancer models that recapitulate the original tumor tissue’s biology and are suitable for high-throughput drug screening. The combination of both platform’s increases the translational relevance of the development pipeline and offers the possibility to enlarge the respective panels of tumor models. Tackling an unmet medical need, we initially created matched mesothelioma PD3D® and PDX models. Mesothelioma is an aggressive cancer with poor prognosis and limited treatment options. Development of new therapies is hampered by shortage of available relevant tumor models. We created PD3D® models from PDX mesothelioma models and vice versa and generated drug sensitivity profiles with standard of care such as Gemcitabine, platinum derivates and a number of targeted agents to confirm their suitability as matched models for future projects. We were able to prove that models express stable histological, phenotypic features and drug sensitivity profiles across the two platforms. With this proof-of-concept study, the feasibility to combine the PD3D® biobank comprising more than 500 models from CELLphenomics with the PDX bank from CRL including 700 PDX models, has gained momentum. In consideration of the changing regulatory landscape, the combination of in vitro and in vivo platforms is a crucial step towards a drug development pipeline that incorporates the principles of 3R and increases its translational value due to fully human technologies being the corner stones of the drug development process. Citation Format: Jürgen Loskutov, Eva Oswald, Lena Wedeken, Christoph J. Reinhard, Julia Schueler, Christian R. Regenbrecht. Mix and match - A comprehensive pipeline for matched patient-derived PDX and PD3D® modelsfor cancer research and preclinical drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 240.