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Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 1941-1949
IL-2 Adenovector-Transduced Autologous Tumor Cells Induce Antitumor
Immune Responses in Patients With Neuroblastoma
Laura Bowman,
Michael Grossmann,
Donna Rill,
Michael Brown,
Wan-yun Zhong,
Barbara Alexander,
Thasia Leimig,
Elaine Coustan-Smith,
Dario Campana,
Jesse Jenkins,
Diane Woods,
Geoffrey Kitchingman,
Elio Vanin, and
Malcolm Brenner
From the Departments of Hematology-Oncology, Pathology, and Virology,
St Jude Children's Research Hospital, Memphis, TN; and the Department
of Pediatrics, University of Tennessee, Memphis College of Medicine,
Memphis, TN.
In many different murine models, the immunogenicity of tumor cells
can be increased by transduction with a range of immunostimulatory genes, inducing an immune response that causes regression of
pre-existing unmodified tumor cells. To investigate the relevance of
these animal models to pediatric malignancy, we used autologous
unirradiated tumor cells transduced with an adenovirus-IL-2 to immunize
10 children with advanced neuroblastoma. In a dose-escalation study, we
found that this tumor immunogen induced a moderate local inflammatory response consisting predominantly of CD4+ T lymphocytes,
and a systemic response, with a rise in circulating CD25+
and DR+ CD3+ T cells. Patients also made a
specific antitumor response, manifest by an IgG antitumor antibody and
increased cytotoxic T-cell killing of autologous tumor cells.
Clinically, five patients had tumor responses after the tumor immunogen
alone (one complete tumor response, one partial response, and three
with stable disease). Four of these five patients were shown to have
coexisting antitumor cytotoxic activity, as opposed to only one of the
patients with nonresponsive disease. These results show a promising
correlation between preclinical observations and clinical outcome in
this disease, and support further exploration of the approach for
malignant diseases of children.
© 1998 by The American Society of Hematology.
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