Abstract
The Epstein–Barr virus (EBV) is associated with lymphomas and carcinomas. For some of these, the adoptive transfer of EBV specific T cells has been therapeutically explored, with clinical success. In order to avoid naturally occurring EBV specific autologous T cell selection from every patient, the transgenic expression of latent and early lytic viral antigen specific T cell receptors (TCRs) to redirect T cells, to target the respective tumors, is being developed. Recent evidence suggests that not only TCRs against transforming latent EBV antigens, but also against early lytic viral gene products, might be protective for the control of EBV infection and associated oncogenesis. At the same time, these approaches might be more selective and cause less collateral damage than targeting general B cell markers with chimeric antigen receptors (CARs). Thus, EBV specific TCR transgenic T cells constitute a promising therapeutic strategy against EBV associated malignancies.
Highlights
Introduction of EBV and Its OncogenesisThe Epstein–Barr virus (EBV) was discovered in 1964, and was the first human tumor virus [1,2].It is still, to date, the most potent pathogen to transform human B cells into immortalized lymphoblastoid cell lines (LCLs) in vitro [3]
As can be seen from the registered clinical trials, these sources of T cells are mainly used for chimeric antigen receptors (CARs) transduction against EBV associated lymphomas, while EBV specific T cell receptors (TCRs) transgenes are mainly explored for EBV associated carcinomas, mainly nasopharyngeal carcinoma (NPC), for which no specific CARs exist that would not cause severe side effects during treatment
While EBNA1, LMP1 and LMP2 have emerged as suitable targets and have even been clinically tested [54,55], the recent realization that early lytic
Summary
The Epstein–Barr virus (EBV) was discovered in 1964, and was the first human tumor virus [1,2]. B cell infection by EBV is the growth transforming latency III, expressing six nuclear antigens (EBNAs) and two latent membrane proteins (LMPs), together with viral non-translated small RNAs (EBERs) and miRNAs (Figure 1) This viral gene expression pattern is found in EBV associated post-transplant lymphoproliferative disease (PTLD), HIV associated immunoblastic lymphoma, some diffuse large B cell lymphomas (DLBCL) and LCLs [9]. While immune suppression is most pronounced early after transplantation and late in HIV infection when immunogenic EBV latency III lymphomas occur, Hodgkin’s and Burkitt’s lymphoma, with restricted viral antigen expression, occur late after transplantation and earlier in HIV infection in the presence of recovered or not yet sufficiently damaged immune responses These considerations suggest that efficient immune responses seem to protect us from EBV associated lymphomas
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