Platform • Frankfurt Cancer Institute

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Molecular Mechanisms

Precision Oncology

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Clinical Translation Programs are the Strategic Core of FCI.

Research in FCI

Clinical Translation Programs
Strategic Core of FCI

Multidisciplinary teams consisting of clinicians, tumor biologists, biochemists, chemists and bioinformaticians work together in these interdisciplinary research projects. The teams rely on the technology platforms provided by the five research areas.

P1
Proteomics & Functional Genomics

The goal of Technology Platform 1 is to find individual parameters that can improve the diagnosis of tumors or better predict the response to therapy. For example, the composition of all proteins in a cell can be qualitatively and quantitatively analyzed by means of mass spectrometry. The measured profile (“proteome”) contains unique information – similar to a fingerprint – and by comparing tumor cells with healthy cells of the same patient, new prognostic and diagnostic criteria can be identified.

P2
Immuno-Oncology

Technology platform 2 Immuno-Oncology uses the innovative cell type-specific gene transfer technologies available at FCI to develop new immunotherapeutic concepts. These include the genetic modification of T lymphocytes or natural killer cells (NKs) with chimeric antigen receptors (CARs) as well as the precise transfer of immunomodulatory agents into tumor tissue. This is complemented by the Immunomonitoring Platform.

P3
Tumor Models

The aim of Technology Platform 3 Tumor Models is to develop new tumor models that can be used to better predict the clinical success of a compound identified in basic research in patients. This platform represents the essential link for the transfer of new therapeutic strategies into the clinic.

P4
Drug Development

The goal of the Technology Platform 4 is to develop new therapeutic approaches and to advance them to the development of new drugs. The extensive chemical, pharmaceutical and structural biology expertise at Goethe University in Frankfurt makes it possible to develop and optimize new drug candidates against validated target structures; innovative biologicals and cell therapeutics are developed at Georg-Speyer-Haus and the Paul-Ehrlich-Institut.

P5
Clinical Translation & Biobank

The integration of clinical trials into the FCI is essential as an endpoint for drug development and a starting point for the investigation of response and resistance mechanisms. The goal is to initiate such studies in close collaboration with the University Center for Tumor Diseases (UCT). The UCT Frankfurt has continuously worked on the expansion of a comprehensive clinical research unit, which will be fully available to the FCI. This ensures the practical implementation of early translational studies at the FCI site.

Discovery & Development

The primary objective of this program is to address excellent hypotheses on basic biological mechanisms of tumorigenesis, progression, diagnosis, and therapy.

P 1

PROTEOMICS & FUNCTIONAL GENOMICS

Tumor cells are changing at tremendous speed. On the one hand, this property promotes their rampant growth and the development of resistance to therapy, on the other hand, it results in no tumor being the same as the other, making reliable prognoses for individual patients often difficult.

IMMUNO-ONCOLOGY

The newly established immuno-oncology platform will use the innovative cell type-specific gene transfer technologies available at FCI to develop new immunotherapeutic concepts. These include the genetic modification of T lymphocytes or natural killer cells (NKs) with chimeric antigen receptors (CARs) as well as the precise transfer of immunomodulatory agents into tumor tissue.

The necessary vector systems have been and are being developed within the FCI by the partner PEI. World-leading in the generation of so-called receptor-targeted vectors, CD4- and CD8-targeted lentiviral vectors have been generated, which can introduce therapeutic genes highly selectively with more than 99% precision into the respective subtypes of T- lymphocytes. This precise gene transfer not only works ex vivo in cultured cells, but also in vivo, in mouse models, the general feasibility of the concept could be demonstrated.

TUMOR MODELS

This platform represents the essential link for the transfer of new therapeutic strategies into the clinic. Far too often, promising compounds fail in later clinical development. The lack of meaningful preclinical models is an important reason for this low success rate. The aim of Technology Platform 3 is therefore to develop new tumor models that can be used to better predict the clinical success of a compound identified in basic research in patients.

Technology Platform 3 focuses primarily on the development and application of patient- derived tumor models (PDX), new techniques for cultivating tumor cells in three- dimensional structures (organoid cultures), and the use of relevant genetically defined mouse models. The close interaction with the biobank of the University Center for Tumor Diseases (UCT) enables early research on the effects to be expected in patients and to obtain decisive indications for further development.

DRUG DEVELOPMENT

The goal of the Technology Platform 4 is to develop new therapeutic approaches and to advance them to the development of new drugs. The extensive chemical, pharmaceutical and structural biology expertise at Goethe University in Frankfurt makes it possible to develop and optimize new drug candidates against validated target structures; innovative “biologicals” and cell therapeutics are developed at Georg-Speyer-Haus and the Paul- Ehrlich-Institut in Langen, for which certified production areas are available at the Institute of Transfusion Medicine.

Since 2017, Goethe University Frankfurt has also been one of the academic sites of the global Structural Genomics Consortium (SGC), a public-private open science partnership with the aim of accelerating drug development by exploiting previously untapped resources. The FCI will collaborate closely on drug discovery with the SGC site in Frankfurt, which has libraries of compounds for potential new applications as well as highly selective inhibitors.

CLINICAL TRANSLATION & BIOBANK

Of particular importance for the FCI are also the clinical scientists of the Technology Platform 5 Clinical Translation and Biobank, who are organized in multicenter study groups for therapy optimization. They assist the FCI project groups with questions of clinical relevance and cover a broad spectrum of indications (gastric, rectal, breast and lung carcinomas, brain tumors, acute lymphoid and myeloid leukemias, multiple myelomas, lymphomas).

Discovery & Development Program

The primary objective of this program is to address excellent hypotheses on basic biological mechanisms of tumorigenesis, progression, diagnosis, and therapy. For example, the proposed projects elucidate the molecular mechanisms of applied or new therapies, define potential target structures in tumors, identify oncogenic mutations, or serve model and method development to expand the repertoire of diagnostic assays, innovative technologies, and preclinical models. In the medium to long term, these projects can lead to a disease-specific clinical translation program.
D&D projects are advertised annually internally and funded by the FCI in the sense of a start-up aid. They should always demonstrate a long-term perspective, which will allow them to attract additional research funding in the future.