TREATMENT AND MODELING OF EPSTEIN-BARR VIRUS POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER

Epstein-Barr virus (EBV) is the etiological agent of infectious mononucleosis and is associated with various diseases such as Burkitt’s lymphoma, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disorder (PTLD). In all of these diseases, the expression of Epstein-Barr virus nuclear antigen 1 (EBNA-1) is common and therefore this viral protein represents a possible therapeutic target. Previous studies have intimated that EBNA-1 auto-inhibits its presentation to the immune system via the expression of a glycine-alanine rich domain that blocks proteasomal degradation. Thus to understand the expression of EBNA-1 and to evaluate the potential of targeting this viral antigen in the context of PTLD, we examined the role of glycine-alanine repeats (GAr) in EBNA-1 protein expression and further investigated the in vivo efficacy of an in-house produced α-EBNA-1 T cell receptor-like monoclonal antibody (α-EBNA-1 TCR-like mAb) using a mouse xenograft model of PTLD. With the aim of translating our findings into studies relevant to humans, we developed and optimized an autologous humanized mouse model for future preclinical evaluations of the antibody

Author dc:creator

• TAN WEI JIAN

• EBV, PTLD, EBNA-1, TCR-like mAb, Humanized mouse