   
The Thoracic Society of Australia & New Zealand
1998 Annual Scientific Meeting - Adelaide, March 15-18
P70
PERSISTENT VACCINIA VIRUS-INTERLEUKIN 2 (VV-IL2)
GENE EXPRESSION IN MALIGNANT MESOTHELIOMA (MM) DESPITE EVIDENCE
OF ANTI-VIRAL IMMUNITY
Sutapa Mukherjee1,
Thomas Haenel1, Robyn
Himbeck1, Michael Epton2,
Richard A. Lake1, Gerry
Harnett3, Peter Phillips3,
Sue Morey4, David Smith3,
Ian Ramshaw5, John Davidson1,
William Musk4 and Bruce
Robinson1
(1) Department of Medicine, University of Western
Australia, Perth, 6009 (2) Telethon TVW Institute for Child Health
Research, (3) Department of Microbiology, PathCentre, (4) Department
of Respiratory Medicine, Sir Charles Gairdner Hospital, (5) Division
of Cell Biology, John Curtin School of Medical Research, A.C.T.,
2601.
Background: MM is an aggressive
tumor which is resistant to all conventional treatments. We have
in vitro evidence that MM may be recognised by the host
immune system and that the presence of interleukin-2 (IL2) augments
the anti-tumor immune response. We instituted a trial of intratumoral
IL2 gene therapy, using vaccinia virus as the vector for cytokine
delivery. Aim: (1) To ascertain whether VV-IL2 can be detected
in tumor biopsies post intratumoral VV-IL2 administration; (2)
To observe the immune response against vaccinia virus; (3) To
detect toxicity associated with VV-IL2 administration; (4) To
determine whether intratumoral T cell infiltration occurs post
VV-IL2 administration. Methods: 7 patients (6 males / 1
female) with subcutaneous MM tumor deposits received a total of
38 injections of intratumoral VV-IL2 (1x107
pfus per dose). Tumor biopsies and blood samples were obtained
on days 0, 1 to 3 and 6 to 8 of each cycle. VV-IL2 mRNA was tested
in tumor biopsies by PCR using VV-IL2 specific primers. Serial
vaccinia virus IgG levels were monitored during treatment. Immunohistochemistry
was performed on tumour biopsies. Results: VV-IL2 mRNA
was detected in tumor biopsies by PCR (50 cycles) and levels were
highest on Days 1 to 3 post VV-IL2 injection and decreased to
pretreatment levels by Day 8. Vaccinia virus IgG levels increased
with treatment in all subjects (titre 1/1280) compared to pretreatment
levels (titre 1/40). No significant toxicity was observed. T cell
infiltrates were present in tumor biopsies post VV-IL2 administration.
Conclusions: Intratumoral expression of VV-IL2 occurs for
one week postinjection in subcutaneous MM deposits, despite the
presence of high titres of vaccinia virus IgG. VV-IL2 administration
leads to intratumoral T cell infiltration. No significant toxicity
was observed. Vaccinia virus is an effective vector for cytokine
delivery in gene therapy.
KeyWords: Malignant mesothelioma,
interleukin 2, vaccinia virus, gene therapy.
Nominations for Awards:
nil
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