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Generation of anti-tumour effector T cells from naïve T cells by stimulation with dendritic/tumour fusion cells.

Abstract：

:Tumour-draining lymph node T cells are an excellent source of effector T cells that can be used in adoptive tumour immunotherapy because they have already been sensitized to tumour-associated antigens in vivo. However, such tumour-specific immune cells are not readily obtained from the host due to poor immunogenicity of tumours and reduced host immune responses. One obstacle in implementation of adoptive immunotherapy has been insufficient sensitization and expansion of tumour-specific effector cells. In this study, we aim to improve adoptive immunotherapy by generating anti-tumour effector T cells from naïve T lymphocytes. We attempted to achieve this by harnessing the advantages of dendritic cell (DC)-based anti-cancer vaccine strategies. Electrofusion was routinely employed to produce fusion cells with 30-40% efficiency by using the poorly immunogenic murine B16/F10 cell line, D5 cells, and DC generated from bone marrow cells. CD62L-positive T cells from spleens of naïve mice and the fusion cells were cocultured with a low concentration of IL-2. After 9 days of culture, the antigen-specific T cells were identified with an upregulation of CD25 and CD69 expression and a downregulation of CD62L expression. These cells secreted IFN-gamma upon stimulation with irradiated tumour cells. Moreover, when transferred into mice with 3-day established pulmonary metastases, these cells with coadministration of IL-2 exhibited anti-tumour efficacy. In contrast, naïve T cells cocultured with a mixture of unfused DC and irradiated tumour cells did not exhibit anti-tumour efficacy. Our strategy provides the basis for a new approach in adoptive T cell immunotherapy for cancer.

journal_name

Scand J Immunol

journal_title

Scandinavian journal of immunology

authors

Ishida A,Tanaka H,Hiura T,Miura S,Watanabe S,Matsuyama K,Kuriyama H,Tanaka J,Kagamu H,Gejyo F,Yoshizawa H

doi

10.1111/j.1365-3083.2007.02012.x

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

546-54

issue

5

eissn

0300-9475

issn

1365-3083

pii

SJI2012

journal_volume

66

pub_type

杂志文章

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