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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-05-1514. This Article Full Text (PDF) All Versions of this Article: 2002-05-1514v1 101/5/1905    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gottschalk, S. Articles by Rooney, C. M Search for Related Content PubMed PubMed Citation Articles by Gottschalk, S. Articles by Rooney, C. M Social Bookmarking                   What's this? Submitted May 23, 2002 Accepted October 7, 2002 Generating CTL against the subdominant Epstein-Barr virus LMP1 antigen for the adoptive Immunotherapy of EBV-associated malignancies Stephen Gottschalk*, Oliver L Edwards, M Helen Huls, Tatiana Goltsova, Alan R Davis, Helen E Heslop, and Cliona M Rooney Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA Department of Medicine, Baylor College of Medicine, Houston, TX, USA Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA * Corresponding author; email: smg{at}bcm.tmc.edu. The Epstein-Barr virus (EBV) encoded LMP1 protein is expressed in EBV-positive Hodgkin's disease and is a potential target for cytotoxic T-lymphocytes (CTL) therapy. However, the LMP1-specific CTL frequency is low and so far the generation of LMP1-specific CTL has required T-cell cloning. The toxicity of LMP1 has prevented the use of dendritic cells (DC) for CTL stimulation and we reasoned that an inactive, non-toxic LMP1 mutant (LMP1) could be expressed in DC and would enable the activation and expansion of polyclonal LMP1-specific CTL. Recombinant adenoviral vectors expressing LMP1 or LMP1 were tested for their ability to transduce DC. LMP1 expression was toxic within 48 hours whereas high levels of LMP1 expression were achieved with minimal toxicity. LMP1 expressing DC were able to reactivate and expand LMP1-specific CTL from three healthy EBV-seropositive donors. LMP1-specific T cells were detected by IFN- ELISPOT assays using the HLA-A2 restricted LMP1 peptide, YLQQNWWTL (YLQ). YLQ-specific T cells were undetectable (<0.001%) in donor PBMC, however after stimulation the frequency increased to 0.5-3.8%. Lysis of autologous target cells by CTL was dependent on the level of LMP1 expression. In contrast the frequency of YLQ-specific CTL in EBV-specific CTL reactivated and expanded using lymphoblastoid cell lines was low and no LMP1-specific cytotoxic activity was observed. Thus LMP1 expression in DC is non-toxic and enables the generation of LMP1-specific CTL for future adoptive immunotherapy protocols for patients with LMP1-positive malignancies such as EBV-positive Hodgkin's disease. Targeting LMP1 in these malignancies may improve the efficacy of current adoptive immunotherapy approaches. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Yvon, M. Del Vecchio, B. Savoldo, V. Hoyos, A. Dutour, A. Anichini, G. Dotti, and M. K. Brenner Immunotherapy of Metastatic Melanoma Using Genetically Engineered GD2-Specific T cells Clin. Cancer Res., September 15, 2009; 15(18): 5852 - 5860. 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