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, Rajiv Khanna*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    112 Citations (Scopus)

    Abstract

    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 LMPI. Human cells infected with this recombinant polyepitope construct were efficiently recognized by LMP-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.

    Original languageEnglish
    Pages (from-to)3150-3156
    Number of pages7
    JournalBlood
    Volume101
    Issue number8
    DOIs
    Publication statusPublished - 15 Apr 2003

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