IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma.
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.
Bowman
L
L
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, USA.
Grossmann
M
M
Rill
D
D
Brown
M
M
Zhong
W Y
WY
Alexander
B
B
Leimig
T
T
Coustan-Smith
E
E
Campana
D
D
Jenkins
J
J
Woods
D
D
Kitchingman
G
G
Vanin
E
E
Brenner
M
M
D000256:Adenoviridae / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007223:Infant; D007376:Interleukin-2 / Q000235:genetics* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008137:Longitudinal Studies; D009447:Neuroblastoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection / Q000276:immunology
D007376:Interleukin-2