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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-10-3092.

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Submitted October 15, 2002
Accepted November 22, 2002

Therapeutic LMP1 Polyepitope Vaccine for EBV-Associated Hodgkin's Disease and Nasopharyngeal Carcinoma

Jai Duraiswamy, Martina Sherritt, Scott Thomson, Judy Tellam, Leanne Cooper, Geoff Conolly, Mandvi Bharadwaj, and Rajiv Khanna*

Division of Infectious Diseases, Queensland Institute of Medical Research, Herston, Qld, Australia
Synthetic Vaccine Laboratory, John Curtin School of Medical Research, Canberra, ANU, Australia

* Corresponding author; email: rajivK{at}qimr.edu.au.

Development of an epitope-based vaccination strategy designed to enhance Epstein-Barr virus (EBV)-specific CD8+ cytotoxic T lymphocytes is increasingly being considered as a preferred approach for the treatment of EBV-associated relapsed Hodgkin's disease (HD) and Nasopharyngeal Carcinoma (NPC). EBV encoded latent membrane proteins, LMP1 and LMP2 are the only target antigens available for therapeutic augmentation of CTL responses in patients with HD and NPC. Here we describe preclinical studies using a recombinant poxvirus vaccine that encodes a polyepitope protein comprising of six HLA A2-restricted epitopes derived from LMP1. Human cells infected with this recombinant polyepitope construct were efficiently recognized by LMP1-specific CTL lines from HLA A2 healthy individuals. Furthermore, immunization of HLA A2/Kb mice with this polyepitope vaccine consistently generated strong LMP1-specific CTL responses to five of the six epitopes which were readily detected by both ex vivo and in vitro assays. More importantly, this polyepitope vaccine successfully reversed the outgrowth of LMP1 expressing tumours in HLA A2/Kb mice. These studies provide an important platform for the development of an LMP-based polyepitope vaccine as an immunotherapeutic tool for the treatment of EBV-associated HD and NPC.


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