Research > Focus C > Work Packages C01
Summary
In order to prioritize the preclinical development of drugs & biologicals (and combinations thereof) according to their pharmacological characteristics, we will screen potentially effective drug candidates for their brain accessibility and confirm blood-brain-barrier permeation in vivo and over time using microdialysis. Drug candidates with insufficient brain access will be subject to drug-delivery development using cell-penetrating liposomes for packaging, which will be re-evaluated for their brain accessibility. Final efficacy evaluation of promising drugs and drug delivery candidates will be based on the UNITE Core Collection of orthotopic preclinical models of different molecular subgroups of glioblastoma.
Task 1
In silico screening of potential drug candidates penetrating the blood-brain-barrier and in vitro efficacy to select potential antitumor activity.
Steps / Workflow
- in silico pre-selection of promising drug candidates against brain tumors
- in vitro efficacy screening
Task 2
Plasma and tissue drug quantification in mouse models using simultaneous drug administrations
Steps / Workflow
- FDA/EMA-compliant development of validated assays for simultaneous quantification of drugs in relevant biological matrices
- Quantification of drug exposure at the site of action
- DMPK analysis of drug candidates
Task 3
Suitability confirmation of the most promising drug candidates and drug delivery candidates using microdialysis
Steps / Workflow
- in vivo assessment of drug disposition using brain and intratumor microdialysis, plasma, and tissue samples (blood-brain permeability)
- definition of concentrationeffect relationship (tumor response, efficacy, potency, and tolerability)
Task 4
Development of methods to increase the accumulation of non-brain-susceptible drugs by lipid-nanoparticles (LNP)
Steps / Workflow
- Preparation of lipidconjugates to target LAT1
- Preparation of LNP formulations that are surface modified
- in vitro evaluation of brain capillary endothelial cell binding and uptake
- Pharmacological evaluation according to task 2 and 3
Task 5
Translational preparation of selected drug candidates
Steps / Workflow
- identification of target indication and efficacy testing
- allometric scaling
- development of study design and dosing schedule
- preparation of scientific advice
Previous funding period
PRINCIPLE INVESTIGATORS
PFISTER, STEFAN, PROF. DR. MED.
Director Preclinical Research
Hopp Children ́s Cancer Center Heidelberg, German Cancer Research Center (DKFZ), Division of Pediatric Neurooncology & Heidelberg University Hospital, Dep. of Pediatric Hematology and Oncology,
Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
A – F
BENDSZUS, MARTIN, PROF. DR. MED.
Chair and Head of Department
University Hospital Heidelberg, Department of Neuroradiology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
BRECKWOLDT, MICHAEL, DR. MED., PH.D
Clinical Resident / Post Doc
University Hospital Heidelberg, Department of Neuroradiology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
BUNSE, LUKAS, DR. MED.
Post Doc
University Hospital Mannheim, Department of Neurology, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
BUNSE, THERESA, NEE SCHUMACHER, DR. RER. NAT.
Post Doc
Heidelberg University, Mannheim Medical Faculty, University Hospital Mannheim, Department of Neurology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
DOKIC, IVANA, DR. RER. NAT.
Postdoctoral reseacher
Heidelberg University Hospital, Division of Molecular and Translational Radiation Oncology Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany
ERNST, AURÉLIE, PD Dr. rer. nat.
Junior Group Leader
Genome Instability in Tumors, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
G – L
GOIDTS, VIOLAINE, DR. BIOL. HUM.
Junior Research Group Leader
German Cancer Research Center, Junior Research Group Brain Tumor Translational Targets, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
HEROLD-MENDE, CHRISTEL, PROF. DR. RER. NAT.
Professor for Experimental Neurosurgery, Division Head
University Hospital Heidelberg, Department of Neurosurgery, Division of Neurosurgical Research, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
HEUER, SOPHIE, MD
Postdoctoral Researcher / Resident
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
HOPF, CARSTEN, PROF. DR. RER. NAT., DIPL.-BIOCHEM.
Head of CeMOS
Hochschule Mannheim, Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Paul-Wittsack-Str. 10, 68163 Mannheim, Germany
Jones, David, Dr.
Group Leader
Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ) & German Cancer Research Center (DKFZ), Pediatric Glioma Research Group, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
KARREMAN, MATTHIA, PHD
Post Doc
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
KESSLER, TOBIAS, DR. MED.
Post Doc / Resident
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Langbein, Lisa, M.P.A.
Project Coordinator
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
LIU, HAI-KUN, PhD
Head of Department
German Cancer Research CenterBrain Cancer Division of Molecular Neurogenetics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
M – R
Malburg, Cara, M. Sc.
Project Coordinator
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
OPITZ, CHRISTIANE, DR. MED.
Division Head
Metabolic Crosstalk in Cancer
German Cancer Research Center
Im Neuenheimer Feld 280,
69120 Heidelberg, Germany
PFISTER, STEFAN, PROF. DR. MED.
Director Preclinical Research
Hopp Children ́s Cancer Center Heidelberg, German Cancer Research Center (DKFZ), Division of Pediatric Neurooncology & Heidelberg University Hospital, Dep. of Pediatric Hematology and Oncology,
Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
PLATTEN, MICHAEL, PROF. DR. MED.
Chairman/Head
Heidelberg University, Mannheim Medical Faculty, Mannheim University Hospital (UMM), Department of Neurology & DKFZ, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
PUSCH, STEFAN, DR. RER. NAT.
Post Doc
University Hospital Heidelberg, Institute of Pathology, Dep. of Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
Ratliff, Miriam, Dr.med., Dipl.-Biol.
Constultant, Department of Neurosurgery
University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University Theodor-Kutzer-Ufer 1-3, 68167 Mannheim
REUSS, DAVID E., PD DR. MED.
Chief Consultant
University Hospital Heidelberg, Department of Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
S – Z
SAHM, FELIX, PROF. DR. DR. MED.
Head of Div. Molecular Neuropathology
University Hospital Heidelberg, Department of Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
Schlesner, Matthias, Dr. rer. nat.
Group Leader
DKFZ, Bioinformatics and Omic Data Analytics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
TURCAN, SEVIN, PH.D
Junior Research Group Leader
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
VOLLMUTH, PHILIPP, PROF. DR. MED., MBA
Head of Section for Computational Neuroimaging
University Hospital Heidelberg, Department of Neuroradiology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
VON DEIMLING, ANDREAS, PROF. DR. MED.
Chair / Head of Department
University Hospital Heidelberg, Institute of Pathology, Department of Neuropathology & DKFZ, Clinical Cooperation Unit Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
WARTA, ROLF, DR. SC. HUM.
Post Doc
University Hospital Heidelberg, Division of Neurosurgical Research, Department of Neurosurgery, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Wick, Wolfgang, Prof. Dr. med.
UNITE Spokesperson & Chairman
University Hospital Heidelberg, Department of Neurology / Neurooncology & DKFZ, Clinical Cooperation Unit Neurooncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
WINKLER, FRANK, PROF. DR. MED.
Managing senior physician / Full professor for experimental neurooncology
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
WITT, OLAF, PROF. DR. MED.
Director Translational Program
Hopp Children’s Cancer Center at NCT Heidelberg (KiTZ) Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
Zuckermann, Marc, PhD
Group Leader
Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Division of Pediatric Neurooncology, Preclinical modeling Group, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
[/av_one_half]
[/av_section]