Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12

被引：0
作者：
K E Siapati
S Barker
C Kinnon
A Michalski
R Anderson
P Brickell
A J Thrasher
S L Hart
机构：
[1] Molecular Immunology Unit,Department of Haematology
[2] Institute of Child Health,undefined
[3] Oncology and Haematology Department,undefined
[4] Royal Free Hospital School of Medicine,undefined
来源：
British Journal of Cancer | 2003年 / 88卷
关键词：
neuroblastoma; interleukin-2; interleukin-12; immunotherapy; nonviral vectors;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Neuroblastoma immunotherapy using cytokine-modified tumour cells has been tested in clinical trials. However, because of the complex nature of antitumour immune responses, a number of therapies may be required for complete tumour eradication and generation of systemic immunity. We report here the improved antitumour effect of two cytokines, interleukin-2 (IL-2) and interleukin-12 (IL-12), when coexpressed by neuroblastoma cell lines. Initially, transfection of human and mouse neuroblastoma cell lines resulted in high expression levels of biologically active IL-2 and IL-12 in vitro. These cytokines when expressed by transfected Neuro-2A cells completely abolished their in vivo tumorigenicity in a syngeneic neuroblastoma model. Vaccination of established tumours with IL-12-producing cells exhibited a clear effect with reduced tumour growth in the presence of IL-2. In vivo depletion studies showed that CD4+ and CD8+ T cells mediate the response against cytokine-producing cells. These results suggest that IL-2 and IL-12, when cotransfected in tumour cells, are effective against established disease and provide a promising immunotherapeutic approach for the treatment of neuroblastoma.
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页码：1641 / 1648
页数：7
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