Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal Carcinoma Treatment

Abstract

Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human population. EBV primarily targets B-lymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC), Burkitt's lymphoma (BL), and Hodgkin's lymphoma (HL). Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development as well as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside.

Partial absence of PD‐1 expression by tumor‐infiltrating EBV‐specific CD8+ T cells in EBV‐driven lymphoepithelioma‐like carcinoma

“…37,38 However, these strategies show moderate efficacy, with toxicity in some cases. 39 In our study, we only detected EBV-specific CD8 + TILs for lytic proteins (BMLF1 and BRLF1). The oncogenic role of EBV has been attributed to the expression of latent genes providing growth and survival benefit to DNA-damaged epithelial cells.…”

Partial absence of PD-1 expression by tumor-specific CD8+T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report

“…Several therapeutic strategies have been developed to induce a cytotoxic CD8 + T cells (CTL) response targeting specifically the latent protein, such as autologous CTL infusion [35], vaccination with EBV-latent vector [36] or pulsed-dendritic cells [37,38]. However, these strategies show moderate efficacy, with toxicity in some cases [39]. In our study, we did not detect CD8 + TILs specific for EBV latent protein among the three epitopes tested (LMP1, EBNA3A, EBNA3B), we only detected EBV-specific CD8 + TILs for lytic proteins (BMFL1 and BRFL1).…”

Role of Epstein–Barr Virus in the Pathogenesis of Head and Neck Cancers and Its Potential as an Immunotherapeutic Target

“…With respect to vaccine development against EBV-associated NPC, the goal seems attainable due to the distinct immune-biology of the virus and its association with the tumor cells ( 89 ). In EBV-associated NPC, EBV-specific proteins should serve as candidate targets for vaccine development and immune modulation ( 90 , 91 ). To this end, the role of therapeutic vaccines has been tested in preclinical and clinical trials with promising results albeit some challenges ( 90 ).…”

“…To this end, the role of therapeutic vaccines has been tested in preclinical and clinical trials with promising results albeit some challenges ( 90 ). The main targets for vaccination strategies in NPC include the EBV-associated proteins LMP1, LMP2, and EBNA1 ( 91 ). Of these latent proteins, LMP2A and EBNA1 are considered the most promising targets for EBV-specific vaccine development due to their high expression levels ( 92 ).…”