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ID 8530
Eprint ID
8530
FullText URL
Thumnail K002867.pdf 113 KB
Title Alternative
野生型p53蛋白質をパルスした末梢血単球由来の樹状細胞によるp53特異的細胞傷害性Tリンパ球の誘導
Author
Tokunaga, Naoyuki
Abstract
PURPOSE: Dendritic cells are the most potent antigen-presenting cells for initiating cellular immune responses. Dendritic cells are attractive immunoregulatory cells for cancer immunotherapy, and their efficacy has been investigated in clinical trials. The tumor suppressor gene p53 is pivotal in the regulation of apoptosis, and p53-based immunization is an attractive approach to cancer immunotherapy because of the accumulation of p53 protein in malignant but not in normal cells. It has been shown that dendritic cells transduced with an adenoviral wild-type p53 (wt-p53) construct mediate the antitumor immune responses against p53-overexpressing tumor cells. We examined whether monocyte-derived human dendritic cells pulsed with the purified full-length wt-p53 protein were also capable of inducing the specific antitumor responses against p53-overexpressing tumors in vitro. EXPERIMENTAL DESIGN: Immature dendritic cells generated in the presence of interleukin-4 and granulocyte/macrophage colony-stimulating factor from monocytes of HLA-A2- or HLA-A24-positive healthy individuals were pulsed with the purified p53 protein. Uptake of p53 protein by human dendritic cells was assessed by Western blotting and immunohistochemical staining using anti-p53 antibody. Induction of p53-specific CTL response was also evaluated by the cytotoxic assay against p53-overexpressing human tumor cells. RESULTS: Both Western blot and immunohistochemical analysis showed the accumulation of p53 protein in human immature dendritic cells. T cells obtained from HLA-A2- or HLA-A24-positive healthy donors were stimulated twice with p53 protein-pulsed dendritic cells and then applied to the cytotoxicity assay against p53-overexpressing target cells. The CTL activity was specific for p53-overexpressing tumor cells and MHC class I restricted. Moreover, the CTL activity generated by p53 protein-pulsed dendritic cells was nearly identical with that induced by adenoviral wt-p53-transduced dendritic cells. CONCLUSIONS: Our results indicate that monocyte-derived human dendritic cells pulsed with the wt-p53 protein could induce the specific antitumor effect against p53-overexpressing tumors and that this in vitro model offers a new and more simple approach to the development of p53-based immunotherapy.
Keywords
p53
Adenovirus vector
Dendritic cells
Immunotherapy
Published Date
2005-03-25
Publication Title
Content Type
Thesis or Dissertation
Grant Number
甲第2867号
Granted Date
2005-03-25
Thesis Type
Doctor of Philosophy in Medical Science
Grantor
岡山大学
Official Url
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15709203&dopt=Abstract
language
日本語
File Version
none
Refereed
Unknown