Predictive Cancer Therapy

Modern, targeted protein therapeutics, such as recombinant antibodies targeting tumor antigens or multifunctional cytokines targeting death receptors hold great promise to advance treatment of presently uncurable diseases, cancer in particular. In addition, through genetic engineering as well as methods of chemistry and material sciences, the generation of novel, multifunctional reagents combining features of these natural defence molecules will open up new avenues of targeted therapies in oncology. The clinical efficacy of such engineered reagents will depend on the optimum combination of their properties at distinct time-space-levels to achieve maximum on-target and minimum off-target activity. The three major levels here to be considered are

• the distribution and pharmacokinetics within the whole organism
• the distribution and enrichment of the drug in the tumor via targeting strategies
• binding to and activation of their respective target molecules and intracellular signalling pathways, leading to e.g. apoptosis of the target cell.

Aspects of this complex system have been intensively investigated, with qualitative assays prevailing in the past, but quantitative methods and mathematical models gaining increasing importance. For example, a wealth of pharmacokinetic data on therapeutic antibodies exist and initial models focusing on aspects of tumor growth are available. However, the clinical assessment of therapeutic activity so far is, by and large, an educated guess and trial and error procedure oriented at patho/physiological phenomena such as minimum biological response and maximum tolerated dose. The establishment of such an integrative, holistic mathematical model of tumor therapy with predictive power appears particularly attractive and helpful for clinical evaluation of all biological/immune therapy concepts because of the complex bioactivities potentially affecting the whole organism. A predictive mathematical model suitable to guide cancer therapeutic strategies is the ultimate goal of the planned project.

University of Stuttgart, Center Systems Biology (CSB), Stuttgart (DE)

University of Stuttgart, IZI, Stuttgart (DE)

University of Stuttgart, IBVT, Stuttgart (DE)

University of Stuttgart, IST, Stuttgart (DE)

University of Stuttgart (DE)

Universität Magdeburg, MaCS, Magdeburg (DE)

Universität Tübingen, Radiologische Klinik, Tübingen (DE)

Robert Bosch Gesellschaft für Medizinische Forschung, Stuttgart (DE)

Celonic GmbH, Jülich (DE)

Bayer Technology Services GmbH, Leverkusen (DE)