Research Report 2000 - MDC

substantial funding from the German
Federal Ministry for Education and
Research (Bundesministerium für
Bildung und Forschung, BMBF) for a
period of 2 x 4 years.
The Good Manufacturing Practice
(GMP) laboratory includes four
laboratories for vector production and
two for analysis and cell culture. The
GMP laboratory is operated in
conjunction with Schering AG and is
also available for use in collaborative
projects with other partners e.g.
biotechnology companies located on
the Campus.
Patient-oriented Research:
Highlights in the Clinics
The Franz Volhard Clinic houses two
departments, the Department of
Cardiology and the Department of
Nephrology/Hypertension. Rainer
Dietz and Friedrich C. Luft are the
respective heads. The Robert Rössle
Clinic encompasses two departments,
the Department of Hematology/
Oncology and the Department of
Oncological Surgery. Bernd Dörken
and Peter M. Schlag are the respective
heads. The four chiefs are fully aware
that the goal of the unique cooperation
with the MDC is to help clinicians
formulate better hypotheses to pose at
the bedside, as well as to expedite the
transfer of basic knowledge into
clinical practice.
In the Franz Volhard Clinic two
cardiologists, Ludwig Thierfelder and
Matthias Friedrich, have teamed up to
investigate arrhythmogenic right
ventricular cardiomyopathy (ARVC).
Usually, the cause for the responsible
cardiac arrhythmia is never identified.
ARVC, which is inherited both as a
dominant and recessive trait, is
responsible for sudden death in young
people. The condition may be more
common than believed because of
new diagnostic tools that can be
applied before symptoms (fatal
ventricular arrhythmias) develop.
With the help of genetic field
working, entire families can be
studied to identify asymptomatic
individuals. Such persons can be
given medication prophylactically or
treated with implantable defibrillators.
In the Franz Volhard Clinic, Jens
Jordan and other clinicians are
studying mechanisms of high and low
blood pressure. The group is studying
a rare form of monogenic
hypertension with brachydactyly.
8
Affected persons also feature as an
additional phenotype, an aberrant
looping posterior-inferior cerebellar
artery, that impinges on the
venterolateral medulla. This so-called
PICA loop could interfere with
baroreceptor reflex signaling. Similar
PICA loops are commonly observed
in patients with primary essential
hypertension, raising the hypothesis
that a new, hitherto unrecognized form
of secondary hypertension exists. The
group has also identified a defect in a
norepinephrine transporter that
interferes with sympathetic function.
In the Robert Rössle Clinic, clinical
scientists are working to offer patients
with renal cell carcinoma, a common
but untreatable malignancy, a better
outlook. A cell line that expresses a
tumor antigen recognized by T cells
from most HLA-A2 positive patients
with renal cell carcinoma has been
genetically modified in cooperation
with Thomas Blankenstein at the
MDC and Dolores Schendel from the
GSF in Munich. The genetically
engineered cancer cell line expresses
costimulatory molecules and
interleukin 7 and can effectively
activate cytotoxic T lymphocytes. It
will be possible to overcome what has
been a major limitation in cancer
vaccines thus far; namely, the
difficulty of monitoring the ongoing
immune response in order to design
powerful vaccine schedules.
A further approach that utilizes the
opportunities offered by recombinant
technology is the generation of
bispecific-single chain antibodies.
Such constructs can target T
lymphocytes to cells that express a
tumor-associated or a tissue-specific
antigen recognized by monoclonal
RRK
FVK
antibodies. In collaboration with Gert
Riethmüller (Dept of Immunology,
Univ. of Munich), Robert Rössle
hematologists are planning a phase I
study for the treatment of lymphoma
patients.
The surgical oncologists at the Robert
Rössle clinic are working on
improving the survival of cancer
patients by improving both diagnosis
and treatment. Recently 3 dimensional
ultrasonography has been developed to
permit characterization of the tumor
extension far better than can be
appreciated by the surgeons visual
skills. Numerous treatment strategies
are being employed to optimize
outcomes. Combined pretreatment
approaches including hyperthermia are
currently under clinical investigation
for esophageal and rectal tumors as
well as for soft-tissue sarcomas. In the
treatment of sarcomas and melanomas
of the extremities, a surgical limb
isolation provides for highly efficient
hyperthermic combination therapies as
a sole curative procedure or with
combined neoadjuvant interventions.
Cytokines, such as tumor necrosis
factor are also being tested as adjuvant
therapies. Finally, in the framework of
the OP 2000 initiative, we are making
sweeping changes in the surgeon’s
work place. Digital data processing,
the fusion of information from
multiple simultaneous sources,
comprehensive virtual presentation of
complex surgical data sets, robotics,
and interactive consultations with
colleagues outside the operating room
will become routine.
Figure 6: Concept of the Berlin-Buch Campus:
basic research (MDC), clinical application
(RRK, FVK) and commercial (BBB) use
are realized in close collaboration.
Berlin - Buch Campus
ROBERT RÖSSLE
CANCER CLINIC
BERLIN-BUCH
FRANZ VOLHARD
CARDIOVASCULAR CLINIC
BERLIN-BUCH
Charité, Humbold University Berlin
Patient Care
Research
and Teaching
MDC BBB
MAX DELBRÜCK CENTER
FOR MOLECULAR MEDICINE
BERLIN-BUCH
Research
and Teaching
BIOMEDICAL
RESEARCH CAMPUS
BERLIN-BUCH GmbH
Technology
Transfer
Research
and Teaching