Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

被引:0
|
作者
J Kayaga
B E Souberbielle
N Sheikh
W J W Morrow
T Scott-Taylor
R Vile
A G Dalgleish
机构
[1] St George’s Hospital Medical School,Department of Oncology
[2] King’s College School of Medicine and Dentistry,Department of Molecular Medicine
[3] Rayne Institute,Department of Medicine
[4] The Lung Unit,Department of Immunology
[5] The Royal Marsden Hospital,undefined
[6] St Bartholomew’s Hospital and the Royal London School of Medicine and Dentistry,undefined
[7] Imperial Cancer Research Fund Laboratory of Molecular Therapy,undefined
[8] ICRF Oncology Unit,undefined
[9] Royal Postgraduate Medical School,undefined
[10] Hammersmith Hospital,undefined
来源
Gene Therapy | 1999年 / 6卷
关键词
allogeneic vaccination; B16-F10 melanoma; GM-CSF;
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中图分类号
学科分类号
摘要
Genetic modification of tumour cells with the GM-CSF encoding gene renders these cells more potent, as autologous tumour cell vaccine, than their wild-type counterparts. However, autologous vaccines are impractical for wide-scale clinical use and we have therefore investigated the efficacy of the GM-CSF genetic modification approach with an allogeneic whole cell tumour vaccine. In this report, we show that the allogeneic K1735-M2 (H-2k) melanoma cell vaccine induces a specific protective anti-tumour response against the syngeneic B16-F10 (H-2b) melanoma tumour in C57BL/6J mice. In vitro T cell work demonstrated that vaccination of animals with the allogeneic cell vaccine generated cytotoxic T cells specific for the autologous tumour. In vivo T cell subset depletion experiments also illustrated that this anti-tumour effect was mediated by both CD4+ve and CD8+ve T cells, suggesting that the allogeneic vaccine may operate through the ‘cross-priming’ phenomenon whereby tumour antigens are processed and presented to T cells by the host’s own antigen presenting cells (APC). Thus, we transduced K1735-M2 cells with a GM-CSF expressing retroviral vector and showed anti-tumour activity of the GM-CSF secreting K1735-M2 cells as a therapeutic vaccine against the syngeneic B16-F10 tumour. Our data imply that GM-CSF genetically modified allogeneic whole cell tumour vaccines could be successful in the clinic. In addition, more potent combination gene therapy strategies could be tested using this therapeutic allogeneic vaccine model.
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收藏
页码:1475 / 1481
页数:6
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