Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Simultaneous immunisation with a Wilms' Tumour 1 epitope and its ubiquitin fusions results in enhanced cell mediated immunity and tumour rejection in C57BL/6 mice

(2012) Simultaneous immunisation with a Wilms' Tumour 1 epitope and its ubiquitin fusions results in enhanced cell mediated immunity and tumour rejection in C57BL/6 mice. Molecular Immunology. pp. 325-331.

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Abstract

Protein fusion to ubiquitin results in its targeting to proteasome and processing through MHC class I pathway. We used this approach to induce cytotoxic T lymphocyte (CTL) response against a MHC class I epitope. Therefore, two known proteasome targeting systems, "ubiquitin fusion degradation" (UFD) and "N-end rule", were used to immunise C57BL/6 mice. Two plasmids encoding an epitope from Wilms' Tumour 1 (WT1-126), fused N-terminally to ubiquitin, were constructed. They were designated as "pUbVVPT" and "pUbGRPT", targeting the fused epitope to UFD and N-end pathways, respectively. A plasmid encoding VVT1-126 without ubiquitin fusion (pPT) was also constructed as control. Three mice groups were immunised using these constructs (UGR, UVV and PT groups). Two other groups received mixed immunisations of pUbVVPT or pUbGRPT plus pPT plasmids (UVV + PT and UGR + PT). All mice received a WT1-126 peptide booster. Lymphoproliferative responses following stimulation with WT1-126 were observed in all immunisation groups, with mice receiving the mixture of plasmids eliciting the highest proliferation (UVV + PT > UGR + PT > PT). Moreover, In vivo cytotoxicity assay results revealed highest specific lysis of target cells in UVV+PT group. Tumour growth was decreased in all immunised groups, and was completely abrogated in UGR + PT group. In addition, T(H)1 type cytokines patterns were detected from all immunised groups and WT1-126-specific IFN-gamma producing lymphocytes were developed in them. These results suggest that the delivery of ubiquitin-fused epitopes along with epitopes alone can be used to optimise the effect of DNA vaccines on the induction of anti-tumour immunity. (C) 2012 Elsevier Ltd. All rights reserved.

Item Type: Article
Keywords: Author Keywords:Leukemia; Cancer vaccine; Ubiquitin; Immunization KeyWords Plus:N-END RULE; DNA VACCINATION; CANCER; VACCINES; IMMUNOGENICITY; TUBERCULOSIS; PEPTIDES; PROTEINS; ADJUVANT; DELIVERY
Page Range: pp. 325-331
Journal or Publication Title: Molecular Immunology
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q2
Volume: 51
Number: 3-4
Publisher: scopus
Depositing User: خانم مریم زرقانی
URI: http://repository.zums.ac.ir/id/eprint/1582

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