MISC

2005年2月

Retroviral vector backbone immunogenicity: identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences

GENE THERAPY
  • E Kondo
  • ,
  • Y Akatsuka
  • ,
  • A Nawa
  • ,
  • K Kuzushima
  • ,
  • K Tsujimura
  • ,
  • M Tanimoto
  • ,
  • Y Kodera
  • ,
  • Y Morishima
  • ,
  • K Kuzuya
  • ,
  • T Takahashi

12
3
開始ページ
252
終了ページ
258
記述言語
英語
掲載種別
DOI
10.1038/sj.gt.3302406
出版者・発行元
NATURE PUBLISHING GROUP

Retroviral vectors are the frequently applied gene delivery vehicles for clinical gene therapy, but specificity of the immunogenicity to the protein encoded by the inserted gene of interest is a problem which needs to be overcome. Here, we describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived from the protein encoded by the retroviral vector backbone, which were established during the course of our attempts to generate CTLs against cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced cells were generated in four out of eight donors by stimulating CD8 T cells with CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL clones derived from one of the CTL lines were found to recognize epitopes from gag in the context of HLA-B* 4403 and -B*4601, respectively. Similarly, an HLA-B* 3501-restricted CTL clone from a cervical cancer patient recognized an epitope located in the junctional regions of the gag and pol sequences. These results show that polypeptides encoded by components of the retroviral vector backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus, potential CTL responses to retroviral products should also be considered in clinical settings.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.1038/sj.gt.3302406
CiNii Resolver ID
http://ci.nii.ac.jp/nrid/9000239248799
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000226468300008&DestApp=WOS_CPL