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<p>Epstein-Barr virus (EBV)-associated B-cell lymphomas pose a therapeutic challenge due to their resistance to conventional chemotherapy and limited efficacy of current targeted approaches. Here, we identified CD80 as a cell surface antigen highly expressed in EBV-positive B-cell lymphomas. Monoclonal antibodies were generated from mice immunized with recombinant human CD80 and subsequently engineered into chimeric formats. These antibodies were evaluated for their cytotoxic activity against CD80-expressing lymphoma cells. Notably, high-affinity clones elicited robust antibody-dependent cellular cytotoxicity (ADCC) but lacked complement-dependent cytotoxicity (CDC), in contrast to rituximab, which targets CD20 and mediates both ADCC and CDC. Our findings suggest that cytotoxic effector functions are regulated not only by the constant region of the antibody but also by the antigen recognized by its variable region. Importantly, these CD80-specific antibodies do not inhibit T cell responses against EBV-positive immortalized cells, highlighting their potential as promising therapeutic candidates for EBV-positive lymphomas and other CD80-expressing malignancies.</p>

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CD80 (B7-1) as a potential therapeutic target in Epstein–Barr virus‑associated B cell diseases

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Rin Yoshizato,
  • Mariko Miura,
  • Yumi Tamura,
  • Yohei Kawano,
  • Yuya Hokama,
  • Nanami Soda,
  • Yusei Ota,
  • Kotomi Yamashita,
  • Taisei Fukushima,
  • Masataka Ishimura,
  • Shouichi Ohga,
  • Tomoharu Yasuda

摘要

Epstein-Barr virus (EBV)-associated B-cell lymphomas pose a therapeutic challenge due to their resistance to conventional chemotherapy and limited efficacy of current targeted approaches. Here, we identified CD80 as a cell surface antigen highly expressed in EBV-positive B-cell lymphomas. Monoclonal antibodies were generated from mice immunized with recombinant human CD80 and subsequently engineered into chimeric formats. These antibodies were evaluated for their cytotoxic activity against CD80-expressing lymphoma cells. Notably, high-affinity clones elicited robust antibody-dependent cellular cytotoxicity (ADCC) but lacked complement-dependent cytotoxicity (CDC), in contrast to rituximab, which targets CD20 and mediates both ADCC and CDC. Our findings suggest that cytotoxic effector functions are regulated not only by the constant region of the antibody but also by the antigen recognized by its variable region. Importantly, these CD80-specific antibodies do not inhibit T cell responses against EBV-positive immortalized cells, highlighting their potential as promising therapeutic candidates for EBV-positive lymphomas and other CD80-expressing malignancies.