Cancer Vaccine and Therapy
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Date
2006-06
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Publisher
The Ohio State University
Abstract
Epstein Barr Virus associated post-transplant lymphoproliferative disorder (EBV/PTLD) is a common and often fatal malignancy in organ transplant patients. The incidence of PTLD has been shown to be directly related to a low frequency of EBV-specific cytotoxic T lymphocytes (CTLs) in patients who receive immunosuppressive therapy to prevent organ rejection.
In our laboratory we have identified, through a chimeric mouse-human model of human PTLD and subsequently in PTLD patients, that the expression an EBV lytic gene named BZLF1 plays an important role in controlling the development of PTLD. We hypothesize that at least one component of the increased incidence of PTLD in this patient population is the patient’s cellular immune deficiency against EBV lytic and latent antigens. A corollary to this hypothesis is that vaccine-enhanced EBV-specific immunity will restore the protection of this malignancy.
Here we demonstrate that a vaccine of BZLF1 protein transduced monocyte-derived antigen presenting cells (dendritic cells) stimulate the expansion of EBV BZLF1-specific CTLs in vitro. Currently we are evaluating the efficacy of this approach in vivo using a chimeric mouse-human model of human PTLD.
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Keywords
Epstein Barr Virus, Post Transplant Lymphoproliferative Disorder