Download An Introduction to DKFZ

An Introduction to DKFZ
Otmar D. Wiestler
Deutsches Krebsforschungszentrum, Heidelberg
Page 1
DKFZ Locations on Campus
Cancer Research @ DKFZ
•
Established in 1964
•
National research center
•
Helmholtz association
•
Location on Heidelberg
biomedical campus
•
Team of 3000 members
•
Funding from BMBF & BW
•
Coordination of national &
international activities
Helmholtz International Graduate
School for Cancer Research
• High quality, comprehensive,
structured and interdisciplinary
graduate training in cancer research
• Vivid interaction with international
partners (Karolinska, MDACC, WIS)
• Cooperation with Universites
and Helmholtz centers
450 graduate students
National Reference Center
for Cancer Information
New and expanding research fields
Cancer genome
Epigenetics, Small regulatory RNAs
Systems biology of cancer & modelling
Angiogenesis
Cancer stem cells
Metabolic dysfunction & cancer
Cancer immunotherapies
Neurooncology
High field MRI, molecular imaging
Particle therapy, radiation biology
Epidemiology, early detection & prevention
Stem cells & Cancer
• Cancers originate from somatic stem or progenitor cells
• Cancer cells with stem cell properties
control tumor growth and biology
• Cancer stem cells serve as a reservoir
for tumor progression and recurrence
DKFZ Cancer Stem Cell Program
Joint activity with the
Dietmar-Hopp-Foundation
Three HI-STEM
Junior Research Groups
Marieke Essers
Michael Milsom
Christoph Rösli
Cancer Genome Consortium
• High number of genomic alterations in cancer cells
• Striking inter-individual variability
• Mutation analysis as basis for individualized treatment
• International Cancer Genome Consortium
Isocitrate dehydrogenases
IDH2
IDH1
cytosolic
mitochondrial
NADP+ specific
NADP+ specific
IDH3A / IDH3B / IDH3G
Mitochondrial NAD+ specific
Andreas von Deimling
Isocitrate dehydrogenase 1
0.500
0.450
untr.
0.400
wt
H
0.350
E
Q
S
0.300
C
V
0.250
L
G
0.200
GFP
0.150
0.100
0.050
0.000
0
5
10
15
20
25
30
35
40
45
IDH1
685
CNS tumors
wt
mut
% mut
Pilocytic astrocytoma WHO grade I (PA I)
41
40
1
2%
Subependymal giant cell astrocytoma WHO grade I (SEGA I)
12
12
0
0%
Pleomorphic xanthoastrocytoma WHO grade II (PXA II)
7
7
0
0%
Astrocytoma WHO grade II (A II)
46
13
34
74%
Anaplastic astrocytoma WHO grade III (A III)
47
18
29
62%
Primary Glioblastoma WHO grade IV (prGBM)
99
92
7
7%
Secondary glioblastoma WHO grade IV (secGBM)
8
1
7
88%
Giant cell glioblastoma WHO grade IV (gcGBM)
8
6
2
25%
Pediatric Glioblastoma WHO grade IV (pedGBM)
14
13
1
7%
Gliosarcoma WHO grade IV (GS)
5
5
0
-
Oligodendroglioma WHO grade II (O II)
51
15
36
71%
Anaplastic oligodendroglioma WHO grade III (O III)
54
18
36
67%
Oligoastrocytoma WHO grade II (OA II)
46
10
36
78%
Anaplastic oligoastrocytoma WHO grade III (OA III)
37
8
29
78%
Myxopapillary ependymoma WHO grade I (E myx I)
6
5
0
-
Ependymoma WHO grade II (E II)
15
15
0
0%
Anaplastic ependymoma WHO grade III (E III)
10
10
0
0%
Medulloblastoma WHO grade IV (MB IV)
58
58
0
0%
Primitive neuroectodermal tumor WHO grade IV (PNET)
9
6
3
33 %
Schwannoma WHO grade I (S I)
17
17
0
0%
Meningioma WHO grade I (M I)
38
38
0
0%
Atypical meningioma WHO grade II (M II)
17
17
0
0%
Anaplastic meningioma WHO grade III (M III)
17
17
0
0%
Pituitary adenoma WHO grade I (PIAD)
23
23
0
0%
Cancer Genome Research
PED-NET
Additional projects :
Early onset
prostate cancer
Malignant lymphoma
Cancer Genome Research
International Cancer
Genome Consortium
DKFZ ultradeep
sequencing facility
Data storage facility
BioQuant & DKFZ
6 petabyte capacity
Cancer genome sequencing
in a diagnostic setting
Peter Lichter,
Roland Eils
Cancer genome sequencing
•
RNA / exome sequencing
• Genome sequencing
Brain tumors
Prostate cancer
Pancreatic cancer
•
Applied bioinformatics
•
Vector insertion analysis
NCT Outpatient
Treatment Unit
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High capacity ultradeep
sequencing facility at DKFZ
Cancer Genome
Research Group
Strategies for Cancer Immunotherapy
T Cell
Therapy
IM M U N OTH ER APY
Breaking
Apoptosis
Resistance
Leukemia
and
Lymphoma
Hepatocellular
Carcinoma
Melanoma
IM M U N OMONITOR IN G
Antibody
Therapy
Vaccination
Strategies
APG101 : First in man
• DKFZ spin off
Extracellular domain of the
human CD95 receptor
• First CD95 ligand blocker
in clinical development
• Specific inhibitor of CD95L
Fc-domain of human IgG
mediated activation
• Well tolerated in phase I
CD95
Ligand
CD95
Cell
FAD
D
Caspases
8/3
PI3
K
AKT/NFkB
Apoptosis Survival
Migration
• Phase II trial in GBM ongoing
• Additional clinical targets
(pancreas, MDS, GvHD)
PREPARATION OF A PHASE I/II CLINICAL TRIAL FOR ONCOLYTIC VIROTHERAPY OF GLIOBLASTOMA MULTIFORME
Jean ROMMELAIRE & Karsten GELETNEKY, DKFZ & University of Heidelberg
Why glioblastoma?
• most common primary
brain tumour
(2-3 % of all human
malignancies)
• dismal
prognosis
(< 5% long term
survivors)
H-1 PV
Preclinical proof of concept
days p.i.
(rat autologous intracranial glioma)
• complete recovery from symptomatic
disease, without signs of toxic or
inflamatory side effects
0
• long term survival without tumour
relapse
1
Survival
rate:
3
H-1
0.5
control
0
10
from: Kleihues, P.,
Kiessling, M., Wiestler,
O.D. (2004)
Trial
20
30
days after implantation
•Target: non-resectable, progressing, malignant non-multifocal glioma (grade IV)
•Design: single center, non-randomized, i.t. dose escalation study
•Objective: assessment of safety and biodistribution of H-1 PV, evidence for antitumoral activity
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7T MRI : a new dimension in medical imaging
Glioblastoma multiforme
7 T: TSE T2
7 T: MR Angiography
7 T MRI : A new dimension in MR imaging
Image guided radiation therapy
•
Artiste : CT-LINAC for IGRT
•
MR-LINAC for IGRT
•
Continuous real time adaptation
of the radiation beam
Heidelberg Ion-Beam Therapy Center
A new era in radiooncology
Enrolling patients since Nov. 2009
•
Image-guided radiotherapy
•
Clinical targets
for particle therapy
•
Ions vs. protons and photons
•
Radiooncology and biologicals
•
Applied radiobiology (modulators of RT)
Prevention is better than cure !
Vaccination against
oncogenic human papilloma viruses :
A milestone in preventive oncology
Nobel prize for Harald zur Hausen 2008
Model projects in preventive oncology
• Early detection of colorectal cancer
• Colorectal cancer in 1st degree relatives
• Metabolic syndrome & cancer
• Physical activity and cancer
• Familial cancers (BRCA, HNPCC)
• National cohort study
National Cohort
• 200,000 adults
•
•
•
•
•
•
(20-70 years)
Multiple regions in Germany
Close cooperation between
Helmholtz centers and
Universities
8 National recruitment
centers
Defined subcohorts
Close collaboration
with universities
Training pograms
North west:
n=30,000
Kiel
Lübeck
Neubrandenburg
Hamburg
Bremen
Hannover
Braunschweig
(HZI)
Münster
Essen
Bochum
Düsseldorf
Halle
Leipzig
Bonn
(DZNE)
Saarland
Mannheim
Heidelberg
(DKFZ)
Regensburg
Augsburg
(HMGU)
Projected age distribution
Berlin (MDC)
Brandenburg
Freiburg
Joint activities & structures
Clinical Cooperation
Units
Immunology
(SFB 938, Alliance)
Junior Research
Groups
Stem Cell Research
(SFB 873, HI-STEM)
Funding for
Tandem Projects
Neurooncology
(NGFN, ICGC)
Funding for MD
Students & Rotations
Imaging
Training Activities
Heidelberg Ion
Therapy (HIT)
Radiooncology
(HIRO)
Translational research requires national efforts
• Translational cancer research facing grand challenges
• Excellent research in German laboratories
• Individual sites not sufficiently competitive
• Lack of coordinated efforts and critical mass
• Translational research requires
novel alliances between the best partners
Translational research programs
Translational research platforms
Consortium School of Oncology
HSO
Provide Education in Clinical Oncology, combining
training on interdisciplinary cancer diagnosis,
patient care and translational cancer research
HSO
Facilitate and improve multidisciplinary,scientific and
clinical interactions between laboratory-based
scientists and clinician scientists
HSO
Establish training programs in translational
research for physicians, physician scientists and
life science experts
HSO
Offer continued medical education for
center physicians, GPs and private practitioners
in oncology
International relationships
30 yrs. DKFZ & MOST / Israel joint funding program
INSERM unit and DKFZ - Canceropolé consortium
Helmholtz units at French INSERM sites
DKFZ & MD Anderson Cancer Center SI agreement
DKFZ & NCI exchange program
DKFZ & Karolinska
DKFZ & NCC Tokyo
DKFZ & Clinica d‘Alemana (Santiago de Chile)
DKFZ & Weizmann Institute joint graduate school
Programs with partners from China, Poland, Tanzania
German-Israeli Helmholtz Research
School in Cancer Biology
DKFZ & NCI, Washington February 2010
DKFZ & Siemens Health Care
A strong R&D alliance
• Integrated Diagnosis & Therapy (IDTZ)
• High field MRI (7T) for oncology
• Molecular imaging
• IT platform
Public Private Partnerships
• Strategic alliance DKFZ & Siemens
• Strategic alliance DKFZ & Bayer Schering Pharma
• Hi-STEM & BioRN
• Spin outs
Apogenix
Progen
mtm
Affimed
Oncology of the Future
•
Molecular diagnosis & stratification
•
Targeted treatments
•
Innovative radiooncology
•
Intelligent combinations
•
Individualized treatment
•
Cancer as chronic disease
•
Cancer prevention
Welcome to the German Cancer Research Center !
Welcome at the DKFZ !