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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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Blood, 15 April 2003, Vol. 101, No. 8, pp. 3150-3156
NEOPLASIA
Therapeutic LMP1 polyepitope vaccine for EBV-associated Hodgkin
disease and nasopharyngeal carcinoma
Jaikumar Duraiswamy,
Martina Sherritt,
Scott Thomson,
Judy Tellam,
Leanne Cooper,
Geoff Connolly,
Mandvi Bharadwaj, and
Rajiv Khanna
From the Cooperative Research Centre for
Vaccine Technology, Tumour Immunology Laboratory, Division of
Infectious Diseases and Immunology, Queensland Institute of Medical
Research and Joint Oncology Program, Department of Molecular and
Cellular Pathology, University of Queensland, Brisbane,
Australia; Synthetic Vaccine Laboratory, John Curtin
School of Medical Research, Australian National University, Canberra,
Australia.
Development of an epitope-based vaccination strategy designed to
enhance Epstein-Barr virus (EBV)-specific CD8+
cytotoxic T lymphocytes (CTLs) is increasingly being considered as
a preferred approach for the treatment of EBV-associated relapsed Hodgkin 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 6 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 5 of the 6 epitopes, which were readily detected by both
ex vivo and in vitro assays. More important, this polyepitope vaccine
successfully reversed the outgrowth of LMP1-expressing tumors 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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