Preclinical models

Innovative Preclinical in vitro and in vivo Models to Better Understand Tumor Diseases

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Circulating tumor cells (CTCs) can migrate out of the blood into other tissues and metastasize there.

Preclinical in vitro and in vivo models are relevant tools for understanding (tumor) diseases and for developing new drugs. In order to successfully translate preclinical results into clinical practice, it is essential that in vitro and in vivo models adequately reflect the particular patient and therapy situation.

To develop tailored models for specific questions, we have established procedures for cell expansion from different patient samples. In addition to models from primary tumors, Fraunhofer ITEM particularly specializes in the generation of innovative preclinical cell models from rare, circulating, and disseminated tumor cells. Moreover, we have also established methods for the ex vivo analysis of cell suspensions representing the cellular composition of various patient samples. This allows complex modes of action of modern drugs and interactions between the tumor and its microenvironment to be tested and explored directly with relevant models.

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To efficiently generate models from clinical samples, different in vitro and in vivo methods are used depending on the sample origin.

Our Preclinical Models

Development of customized preclinical models from patient samples

We use expansion conditions optimized for specific tumor entities to generate preclinical models from clinical samples. The established models are thoroughly characterized in comparison to the patient sample at the phenotypic and genomic levels across multiple passages.

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Established models by expansion method and tumor type (SCLC = small cell lung cancer; NSCLC = non-small cell lung cancer).

Models from disseminated and circulating tumor cells

Disseminated tumor cells (DTCs) are rare metastatic progenitor cells that can be found in distant organs of cancer patients. Due to their immense importance in the development of systemic cancers and despite their low frequency, we have developed and carefully characterized preclinical models of various tumor types and organs from these cells. These rare models offer a unique opportunity to identify novel biomarkers and targets for early-stage systemic cancer treatment and to test adjuvant treatment strategies on relevant metastasis-triggering cells.

Circulating tumor cells (CTC) are rare cells found in the bloodstream that are thought to represent various metastatic colonies in cancer patients. This is the reason why they are target cells of systemic cancer therapies.

At Fraunhofer ITEM in Regensburg, we have established and characterized a large number of preclinical CTC models from liquid biopsies. They are a useful tool for establishing diagnostic or molecular analysis workflows or for testing the efficacy of drugs or their combinations in relevant target cells.

 

Grafik; BU: The isolating of circulating tumor cells (CTC) from blood and disseminated tumor cells (DTC) from tissues such as bone marrow or lymph nodes serves the researchers as a starting point for project-specific innovative preclinical cell models.

Platform for Ex-Vivo Drug Response Assays (PEDRA)

We have developed a Platform for Ex-Vivo Drug Response Assays (PEDRA) that mirrors the clinical patient situation in vitro by using disease-specific models generated from clinical samples, recruited individually for each project. PEDRA comprises several ex-vivo assays of variable cellular complexity. In combination with state-of-the-art readouts drug safety and efficacy can be assessed for a broad range of anticancer treatments. Because PEDRA preserves the original cellular composition of the organ of interest, it is ideal for testing novel IO therapies incl. CPI and ADC.

© Fraunhofer ITEM, Tonia Bargmann
PEDRA: Disease-specific, patient-derived models for preclinical testing of anti-cancer therapies

Patient-derived metastatic niche models

Healthy cells of the body actively communicate with tumor cells and can thereby significantly influence the growth, metastasis, and even the therapy response of a patient. Novel therapies, such as cancer immunotherapies, often influence these interactions in order to eliminate cancer cells. Using our methods, we are able to investigate these corresponding mechanisms and test intervention therapies directly on patient material.

To do this, we use various clinical samples both from solid tumors and malignant effusions (fluid accumulations from cancer, immune and connective tissue cells as an inflammatory response to a tumor in adjacent body cavities) as well as from metastatic organs such as lymph nodes and bone marrow. What is important is that the cells of the patient’s microenvironment remain contained and thus optimally represent the disease situation. In such cases, our flexible assays make not only drug testing with high-throughput confocal microscopy possible but also the investigation of complex mechanisms of cancer using multiplex flow cytometry, cytokine determination, live cell microscopy, or sequencing. 

Contact

Christian Werno

Contact Press / Media

Dr. Christian Werno

Manager of the Working Group on Preclinical Therapy Models

Christopher Jakobs

Contact Press / Media

Dr. Christopher Jakobs

Business Development for Personalized Tumor Therapy

Phone +49 152 28220636