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Background <p>Cytomegalovirus (CMV) infection, with limited therapeutic options, represents a significant complication following transplantation. T cell receptor (TCR)-like antibodies that can recognize and bind to viral peptides presented by the human leukocyte antigen (HLA) show promise for specifically targeting and eliminating CMV-infected cells. Here, we show that this humanized TCR-like antibody efficiently targets CMV-infected cells, thereby supporting the development of this novel and effective therapeutic option for patients.</p> Methods <p>Using a synthetically produced pCMV-pp65<sub>495 − 503</sub>/HLA-A2 as an antigen, we screen for specific antibodies against pCMV-pp65<sub>495 − 503</sub>/HLA-A2 and design a humanized TCR-like antibody. The affinity of the antibody for the pCMV-pp65<sub>495 − 503</sub>/HLA-A2 complex was validated using ELISA, surface plasmon resonance analysis, and flow cytometry. Additionally, its anti-CMV activity was further confirmed in both in vitro assays and animal models.</p> Results <p>In this study, we produced and characterized a TCR-like antibody, 3D7, specific for the pCMV-pp65<sub>495 − 503</sub>/HLA-A2 complex. The humanized form of this antibody, hu3D7, demonstrated high efficiency in targeting and eradicating CMV-infected cells, showing substantial anti-CMV activity both in vitro and in animal models. We demonstrate that hu3D7 exerts its antiviral effect by activating CD8<sup>+</sup> T cells, releasing granzyme B and perforin.</p> Conclusions <p>In conclusion, the TCR-like antibody targeting pCMV-pp65<sub>495 − 503</sub>/HLA-A2 that we developed demonstrated effective recruitment and activation of T cells to kill CMV-infected cells in both in vitro experiments and animal models, showing good potential for anti-CMV treatment. These findings highlight the potential of TCR-like antibodies in treating CMV infections, supporting a promising novel therapeutic strategy for managing post-transplant CMV complications.</p>

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T cell receptor-like antibody specifically targets and eliminates cells infected with cytomegalovirus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Dabing Chen,
  • Caidong Hu,
  • Yunda Hong,
  • Jingjing Xu,
  • Jiaqi Sun,
  • Jinhua Ren,
  • Yangtao Wu,
  • Ningshao Xia,
  • Quan Yuan,
  • Jianda Hu,
  • Ting Yang

摘要

Background

Cytomegalovirus (CMV) infection, with limited therapeutic options, represents a significant complication following transplantation. T cell receptor (TCR)-like antibodies that can recognize and bind to viral peptides presented by the human leukocyte antigen (HLA) show promise for specifically targeting and eliminating CMV-infected cells. Here, we show that this humanized TCR-like antibody efficiently targets CMV-infected cells, thereby supporting the development of this novel and effective therapeutic option for patients.

Methods

Using a synthetically produced pCMV-pp65495 − 503/HLA-A2 as an antigen, we screen for specific antibodies against pCMV-pp65495 − 503/HLA-A2 and design a humanized TCR-like antibody. The affinity of the antibody for the pCMV-pp65495 − 503/HLA-A2 complex was validated using ELISA, surface plasmon resonance analysis, and flow cytometry. Additionally, its anti-CMV activity was further confirmed in both in vitro assays and animal models.

Results

In this study, we produced and characterized a TCR-like antibody, 3D7, specific for the pCMV-pp65495 − 503/HLA-A2 complex. The humanized form of this antibody, hu3D7, demonstrated high efficiency in targeting and eradicating CMV-infected cells, showing substantial anti-CMV activity both in vitro and in animal models. We demonstrate that hu3D7 exerts its antiviral effect by activating CD8+ T cells, releasing granzyme B and perforin.

Conclusions

In conclusion, the TCR-like antibody targeting pCMV-pp65495 − 503/HLA-A2 that we developed demonstrated effective recruitment and activation of T cells to kill CMV-infected cells in both in vitro experiments and animal models, showing good potential for anti-CMV treatment. These findings highlight the potential of TCR-like antibodies in treating CMV infections, supporting a promising novel therapeutic strategy for managing post-transplant CMV complications.