Holistic Multi-Scale Modeling of Targeted Protein Therapeutics Action: Towards Predicting Effective Treatment of Cancer

Prof. K. Pfizenmaier
Stuttgart Research Center Systems Biology
Universität Stuttgart
Funding Period:

01/01/2013 – 31/12/2015

Project description:
Development of targeted therapeutics for treatment of complex diseases requires ultimately a mechanistic understanding of the governing processes and interactions within the body, ideally supported by a predictive computational model. Targeted protein therapeutics, such as tumor specific antibodies or cytokines targeting death receptors hold great promise to advance treatment of presently non-curable diseases, cancer in particular. Through genetic engineering as well as methods of chemistry and material sciences, the generation of novel, multifunctional reagents combining features of these natural defense molecules will open up new avenues of targeted therapies in oncology. The clinical efficacy of such engineered reagents, given as monotherapy or in combination with standard drugs, will depend on their optimum application at distinct time-space-levels to achieve maximum on-target (i.e. therapeutic) effects while minimizing off-target activity. The project PREDICT takes a systems biology approach towards an improvement of cancer therapy with this new class of reagents, applying combined experimentation and mathematical modeling to reach a holistic understanding of the action of targeted therapeutics and to guide their clinical development.
Subproject 1

Design, Herstellung und Wirksamkeits­prüfung von tumorselektivenProteintherapeutika
Kontermann, Pfizenmaier (University of Stuttgart

Subproject 2

Zelluläre Interaktion, Ausbildung von Signalkomplexen und crosstalk-Mechanismen der intrazellulären Signaltransduktion ErbB-gerichteter TRAIL-Rezeptor aktivierender Fusionsproteine
Scheurich, Olayoiye (University of Stuttgart)

Subproject 3

Radiomarkierung und Multipara­metri­sche Bildgebung von TRAIL-Fusions­proteinen
Pichler (University of Tübingen)

Subproject 4

Ex-vivo Untersuchungen zur Gewebe­verteilung und primärer Wirkung therapeutischer Proteine in Tumoren des Darms und des Peritoneums
Schwab, Mürdter (Robert Bosch Gesellschaft IKP)

Subproject 5

Therapeutikatransport in vaskulari­sier­ten Tumoren in Xenograft-Modellen
Reuss (University of Stuttgart)

Subproject 6

Modellierung und systemtheoretische Analyse des Cross- talk intrazellulärer Signalwege bei Behandlung mit tumorselektiven Proteintherapeutika und Ankopplung an die Gewebe- und Organebene
Allgöwer (University of Stuttgart)

Subproject 7

Therpeutikatransport und Wirkung in vaskularisiertem Kolonkarzinom
Helmig (University of Stuttgart)

Subproject 8

Design, Herstellung und Wirksam­keits­prüfung von tumorselektiven Protein­therapeutika
Herrmann, Celonic GmbH

Subproject 9

Umsetzung der Modelle in die klinische Anwendung
Küpfer, Eissing (Bayer Technology Services (BTS))

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