EBV Conference 2008 Guangzhou - Baylor College of Medicine

211 (RegID: 1141)
Graham Taylor
Institution: Department of Oncology, Johns Hopkins University School of Medicine
e-mail: dfu1@jhmi.edu
VACCINATION OF PATIENTS WITH EPSTEIN-BARR VIRUS (EBV) POSITIVE
MALIGNANCY WITH MODIFIED VACCINIA ANKARA EXPRESSING A CHIMAERIC EBV
EBNA 1 AND LMP2 ANTIGEN
Graham Taylor 1, Edwin Hui 2, Anthony Chan 2, Kevin Harrington 3, Alan Rickinson 1, Neil Steven 1
Posterabstract
Epstein-Barr virus is present within the malignant cells of several human cancers including almost all
undifferentiated nasopharyngeal carcinoma (NPC) and 40% Hodgkin’s lymphoma. In malignant cells,
viral latent antigen expression is restricted to EBNA1, LMP2 and LMP1 whereas immunodominant
targets for MHC class I restricted T cell responses are down-regulated. The EL vaccine encodes a fusion
gene comprising EBNA1 c terminal 363-641 spliced to complete LMP2. This includes multiple MHC
class I restricted epitopes in LMP2 known to be recognised by low abundance circulating cytotoxic T
lymphocytes in some healthy donors and cancer patients, and also several MHC class II restricted epitopes
in EBNA1.
To determine immunogenicity, a UK-based trial is recruiting patients with any EBV+ cancer outside the
transplant setting, following one program of primary chemotherapy or chemoradiotherapy, in remission or
for whom no other standard therapy exists. In parallel, in China a trial with the same design is recruiting
NPC patients following first line therapy. These trials escalate from 5x10^7 to 5x10^8 pfu virus given
intradermally three times at three week intervals. Seven and ten patients have been treated in the UK and
China respectively and dosage has so far reached 3.3x10^8 pfu. The main toxicities have been injection
site reactions and systemic ‘flu like symptoms. Immune responses characterised to date indicate
amplification of CD8+ T cell responses to LMP2 as well as CD8+ and CD4+ T cell responses to EBNA1
in a high proportion of vaccinated patients.
EBV Conference 2008 Guangzhou
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