Abstract
Latent Epstein-Barr virus (EBV) infection is associated with several types of cancer. Several clinical studies have targeted EBV antigens as immune therapeutic targets with limited efficacy of EBV malignancies, suggesting that additional targets might be important. BamHI-A rightward frame 1 (BARF1) is an EBV antigen that is highly expressed in EBV+ nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC). BARF1 antigen can transform human epithelial cells in vivo. BARF1-specific antibodies and cytotoxic T cells were detected in some EBV+ NPC patients. However, BARF1 has not been evaluated as an antigen in the context of therapeutic immunization. Its possible importance in this context is unclear. Here, we developed a synthetic-DNA-based expression cassette as immunotherapy targeting BARF1 (pBARF1). Immunization with pBARF1 induced potent antigen-specific humoral and T cell responses in vivo. Immunization with pBARF1 plasmid impacted tumor progression through the induction of CD8+ T cells in novel BARF1+ carcinoma models. Using an in vivo imaging system, we observed that pBARF1-immunized animals rapidly cleared cancer cells. We demonstrated that pBARF1 can induce antigen-specific immune responses that can impact cancer progression. Further study of this immune target is likely important as part of therapeutic approaches for EBV+ malignancies.
Highlights
Epstein-Barr virus (EBV), known as human gammaherpesvirus 4 (HHV-4), is highly ubiquitous, with more than 95% of the world’s population infected by EBV.[1]
It contains an N-glycosylation on asparagine 95 (Asn95), which is important for protein folding and secretion and an O-glycosylation on threonine 169 (Thr169)
Mice with CD8+ T cell depletion completely lost tumor control and exhibited a high tumor burden similar to the controls (Figure 5B), suggesting that CD8+ T cells are DISCUSSION Here, we provide the first study on the immune impact of BamHI-A rightward frame 1 (BARF1) in a mouse immunotherapy model
Summary
Epstein-Barr virus (EBV), known as human gammaherpesvirus 4 (HHV-4), is highly ubiquitous, with more than 95% of the world’s population infected by EBV.[1]. While there have been many studies, there is currently no EBV-targeted immune therapy approved for NPC or EBVaGC
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