Epstein-Barr virus (EBV) is a virus that widely infects humans. After infection, it establishes latency in B cells and persists in the body for life. Although normally controlled by the immune system, immune abnormalities can lead to various conditions, including B-cell lymphoma, various cancers, and lymphoproliferative disorders.
In particular, conditions such as chronic active EBV disease (CAEBV), which is a state where the virus continues to actively multiply in the body over a long period, and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which is a severe illness triggered by viral infection where the immune system becomes overactive, are accompanied by severe inflammation and immune abnormalities, often following a life-threatening, critical course. In these diseases, controlling EBV-infected cells is difficult, and effective treatments other than hematopoietic stem cell transplantation remain limited.
A research group including Professor Tomoharu Yasuda of the Department of Immunology, Graduate School of Biomedical and Health Sciences at Hiroshima University, has discovered "CD80" as a molecule that could serve as a new therapeutic target in EBV-associated B-cell diseases. The results were published in Scientific Reports.
(A) CD80 transcriptional expression levels in a dataset of 16 EBV-positive cell lines and a dataset of 12 normal B-cell lines.
(B) Cell surface CD80 expression in EBV-positive B-lymphoma cell lines (Raji cells) and lymphoblastoid cell lines (LCLs) established from PBMCs derived from healthy individuals. We confirmed that the signal was absent in CD80-knockout (KO) cells.
(C) CD80 expression levels in normal tissues. Specific CD80 expression was observed in lymphoid tissues such as the tonsils, lymph nodes, appendix, spleen, thymus, and bone marrow, as well as in antigen-presenting cells such as Langerhans cells, monocytes, B cells, and macrophages.
Provided by Hiroshima University
In the treatment of B-cell lymphoma, the antibody drug rituximab, which targets a molecule called CD20 on the surface of cancer cells, is used. However, issues exist: some cases do not show sufficient therapeutic efficacy with rituximab, and strongly activating the complement system can induce an excessive systemic inflammatory response. Thus, searching for new therapeutic targets has become a critical challenge.
The research group first comprehensively analyzed membrane proteins specifically expressed in EBV-positive B-cell lymphoma and revealed that CD80 is significantly overexpressed compared to normal B cells and EBV-negative lymphoma. Furthermore, high expression of CD80 was also confirmed in lymphoblastoid cell lines (LCLs) established through EBV infection, and its expression was shown to be localized mainly to lymphoid tissues and antigen-presenting cells. These results suggested that CD80 could be a highly selective and promising therapeutic target.
Next, they generated monoclonal antibodies against CD80 and confirmed that these antibodies specifically bind to the CD80 molecule and CD80-expressing lymphoma cells. Furthermore, they confirmed that these CD80-specific antibodies strongly induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against EBV-positive lymphoma Raji cells and autologous EBV-infected LCLs. Additionally, ADCC activity driven by CD80-recognizing antibodies was consistently confirmed in analyses using PBMCs derived from multiple donors.
On the other hand, complement-dependent cytotoxicity (CDC) was hardly induced. Furthermore, experiments using an antibody where the antigen-binding site of rituximab was replaced from CD20 to CD80 revealed that even antibodies originally possessing CDC activity lost their CDC activity when targeting CD80. These results suggest that the effector function of an antibody can depend heavily not only on the Fc region but also on the structure and characteristics of the target antigen.
CD80 is an important costimulatory molecule that promotes T-cell activation and proliferation by interacting with CD28 on T cells and PD-L1 on antigen-presenting cells. Therefore, it was thought that antibodies targeting CD80 might inhibit T-cell functions responsible for tumor immunity while eliminating tumor cells.
Thus, when examining whether anti-CD80 antibodies inhibit T-cell responses to EBV-infected cells, it was revealed that although CD8-positive T-cell proliferation was slightly reduced in the presence of anti-CD80 antibodies, the T-cell proliferative response to EBV-infected cells was maintained.
These results suggest that while anti-CD80 antibodies effectively eliminate tumor cells, anti-tumor immunity can be maintained.
This study demonstrated that antibody therapy targeting CD80 could serve as a new therapeutic strategy for EBV-associated diseases. In particular, it holds potential for application as a new treatment for refractory diseases with limited current treatment options, such as CD80-expressing lymphomas for which existing drugs are ineffective, CAEBV, and EBV-HLH.
Moving forward, progress toward clinical application is expected through further validation using patient-derived cells, evaluation of efficacy and safety in animal models, and expansion into antibody-drug conjugates (ADCs).
Journal Information
Publication: Scientific Reports
Title: CD80 (B7-1) as a potential therapeutic target in Epstein-Barr virus‑associated B cell diseases
DOI: 10.1038/s41598-026-55043-5
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.