ESVIM/ECVIM Congress 2002
2002 Annual Scientific Meeting of
the European Society of Veterinary Internal Medicine -
Companion Animal
September 19 - 21, Munich Germany
Screening
of cats with Fibrosarcoma for clinical trials – experience of 250 cases
T.
Brill3, J.
Ludwig1, S. Wieland1, K. Wiedmann1, N.
Kjaergaard1, S. Schlemmer1, A. Löcher1, M. Müller-Heidelberg4
, R. Köstlin2, J. Henke3, J. Hirschberger1
Department of Veterinary Internal Medicine1 and Department
of Veterinary Surgery2, Ludwig-Maximillians-University Munich;
Institute of Experimental Oncology3, Technical University Munich,
Transgene4 SA, Strasbourg
With
the goal of elongating the tumour free survival time in fibrosarcoma bearing
cats we examined the efficiency of an adjuvant immunostimulating gene therapy
to the surgical standard therapy. We carried out three phase I-dose escalation
studies and two phase II-clinical trials.
Before
a patient could be enrolled into one of these protocols the cat must be
screened according to a standardised procedure to evaluate fitting to the
inclusion criteria. After clinical examination (Department of Veterinary
Internal Medicine and Surgery) and questioning the owners, blood parameters
(hematological and biochemical status) were tested, followed by ultrasound and
x-ray examination. Due to the planed immunostimulating gene therapy and the
follow up time of one year the owners had to accept a surgery and a gene
transfer protocol and the cats must have a tumour-unrelated life expectancy of
more than one year. Also the absence of a previous immunomodulating treatment
(e.g. use of corticosteroides) or a previous gene therapy has to be stated.
We screened 250 fibrosarcoma bearing cats and could include 180 into the clinical protocols. The main reasons for rejecting a patient were: detection of metastasis, status of non-operability, severe non-cancerous diseases (diabetes, renal failure, heart disease).
PHASE I CLINICAL STUDY OF GM-CSF IN THE ADJUVANT
THERAPY OF FELINE FIBROSARCOMAS
N. Kjaergaard1,
K. Wiedmann1, T. Brill3, R. Köstlin2, J.
Ludwig1, S. Wieland1, J. Henke3, U.
Schillinger3, B. Gänsbacher3, J. Hirschberger1
I. Veterinary Clinic of Internal Medicine1 and Clinic of
Surgery2, Ludwig-Maximillians-University Munich; Institute of
Experimental Onkology3, Technical University Munich
In-vivo-transfection of established tumors with cytokine genes results
in an immune response which is targeted against the tumor cells. For this gene
transfer superparamagnetic iron particles coated with polyethylenimine were
used. Plasmids (pDNA) coding for granulocyte-macrophage-colony-stimulating-factor
(GM‑CSF) were bound to these particles by electrostatic interaction.
Biologically active zones of fibrosarcomas were injected twice under the
influence of a neodymium-iron-boron-magnet (NIB-Magnet) before surgical
removal which is still essential to a successful therapy. The main aim of this
injection is the transfer of the GM-CSF gene into biologically active tumor
cells and therefore a local production of GM-CSF. This cytokine causes a
higher rate of development and differentiation of granulocytes and
macrophages, enhances the presentation of tumor antigens to T-lymphocytes and
can induce cytotoxicity of macrophages. The enhanced immune response should
help to either erase or retain growth of tumor cells which remain after
surgical removal of the tumor and should result in significantly longer
relapse free periods. In this clinical trial nine cats were treated in doses
from 50 to 1250 µg pDNA. In each case three cats received doses of 50 µg,
250 µg and 1250 µg pDNA. During the phase of therapy clinical, hematological
and biochemical parameters were recorded in a common-toxicity-criteria table (CTC-Table)
and judged for the compatibility. 1250 µg pDNA was found to be the maximum
tolerated dose in this method of gene therapy.
