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
PFISTER, STEFAN, PROF. DR. MED.
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
Members
MEMBERS
UNITE brings together physician-scientists and scientists from the Heidelberg University Hospital, the University Hospital Mannheim, the German Cancer Research Center and the Hochschule Mannheim. By combining the complementary research strengths and technological prowess of all participating principle investigators, UNITE will generate considerable added value towards precision neurooncology.
In total, 31 physician-scientists and scientists from the Heidelberg and Mannheim campus provide complementary expertise for the proposed translational focus of the UNITE research program. This will enable practice changes by translating basic research findings into clinical application. Importantly, the integration of 13 junior work package leaders highlights the career development aspect of the initiative.
A – F
ABDOLLAHI, AMIR, DR. MED., DR. RER. NAT.
Heidelberg University Hospital, Division of Molecular and Translational Radiation Oncology Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany
BENDSZUS, MARTIN, PROF. DR. MED.
University Hospital Heidelberg, Department of Neuroradiology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
BRECKWOLDT, MICHAEL, DR. MED., PH.D
University Hospital Heidelberg, Department of Neuroradiology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
BUNSE, LUKAS, DR. MED.
University Hospital Mannheim, Department of Neurology, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
BUNSE, THERESA, NEE SCHUMACHER, DR. RER. NAT.
Heidelberg University, Mannheim Medical Faculty, University Hospital Mannheim, Department of Neurology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
DOKIC, IVANA, DR. RER. NAT.
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.
Genome Instability in Tumors, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
G – L
GOIDTS, VIOLAINE, DR. BIOL. HUM.
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.
University Hospital Heidelberg, Department of Neurosurgery, Division of Neurosurgical Research, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
HEUER, SOPHIE, MD
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
HOPF, CARSTEN, PROF. DR. RER. NAT., DIPL.-BIOCHEM.
Hochschule Mannheim, Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Paul-Wittsack-Str. 10, 68163 Mannheim, Germany
Jones, David, Dr.
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
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
KESSLER, TOBIAS, DR. MED.
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Langbein, Lisa, M.P.A.
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
LIU, HAI-KUN, PhD
German Cancer Research CenterBrain Cancer Division of Molecular Neurogenetics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
M – R
Malburg, Cara, M. Sc.
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
OPITZ, CHRISTIANE, DR. MED.
Metabolic Crosstalk in Cancer
German Cancer Research Center
Im Neuenheimer Feld 280,
69120 Heidelberg, Germany
PFISTER, STEFAN, PROF. DR. MED.
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.
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.
University Hospital Heidelberg, Institute of Pathology, Dep. of Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
Ratliff, Miriam, Dr.med., Dipl.-Biol.
University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University Theodor-Kutzer-Ufer 1-3, 68167 Mannheim
REUSS, DAVID E., PD DR. MED.
University Hospital Heidelberg, Department of Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
S – Z
SAHM, FELIX, PROF. DR. DR. MED.
University Hospital Heidelberg, Department of Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
Sahm, Katharina, Dr. med.
Medical Center Mannheim, Department of Neurology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
Schlesner, Matthias, Dr. rer. nat.
DKFZ, Bioinformatics and Omic Data Analytics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
TURCAN, SEVIN, PH.D
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
VOLLMUTH, PHILIPP, PROF. DR. MED., MBA
University Hospital Heidelberg, Department of Neuroradiology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
VENKATARAMANI, DR. MED., DR. RER. NAT.
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
VON DEIMLING, ANDREAS, PROF. DR. MED.
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.
University Hospital Heidelberg, Division of Neurosurgical Research, Department of Neurosurgery, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Wick, Wolfgang, Prof. Dr. med.
University Hospital Heidelberg, Department of Neurology / Neurooncology & DKFZ, Clinical Cooperation Unit Neurooncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
WINKLER, FRANK, PROF. DR. MED.
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
WITT, OLAF, PROF. DR. MED.
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
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
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Address
Im Neuenheimer Feld 400
69120 Heidelberg
Themen
Research
- Focus A
- A01: Targeting tumor cell network communication to overcome primary and adaptive resistance in glioblastoma
- A02: Development of a specific combination therapy for histone H3-mutant pediatric glioblastoma
- A03: Deciphering resistance against targeted treatments
- A04: Elucidating tumor-associated microglia interactions in astrocytomas CNS WHO-grade 4
- A05: Predictive biomarkers for MGMT-promoter-methylated glioblastoma (2019 – 2023)
- A06: Resistance mechanisms of glioblastoma against alkylating agents and radiotherapy
- A07: Mapping and targeting neuron-tumor networks to tackle therapy resistance in glioblastoma
- A08: Personalized glioblastoma treatment guided by patient-derived tumor organoids
Research
- Focus B
- B01: Mechanisms of response and resistance to glioma-specific t cells
- B02: DNA mis-match repair regulates immune checkpoint blockade therapy in glioblastoma (2019 – 2023)
- B03: Targeting immunosuppressive programs in isocitrate dehydrogenase mutant gliomas
- B04: Impact of myeloid cells on the adaptive immune response in newly diagnosed and recurrent glioblastomas
- B05: Dissecting the response of glioblastoma and its tumor microenvironment to focused high-dose radiotherapy (2019 – 2023)
- B06: Visualization and characterization of immune responses in H3K27M mutant gliomas
Research
- Focus C
- C01: Comprehensive preclinical pharmacology testing of drugs used for glioblastoma treatment
- C02: Radiomics, radiogenomics and deep-learning in neurooncology
- C03: Imaging immune signatures of glioma response and resistance towards immunotherapy (2019 – 2023)
- C04: Metabolic signaling in glioblastoma: a spatial multi-omics approach
- C05: Overcoming glioma radio-resistance with particle therapy
- C06: Functional characterization of EGFR structural variants associated with long-term survival in glioblastoma, IDH-WT