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

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.

Using a synthetically produced pCMV-pp65_{495 - 503}/HLA-A2 as an antigen, we screen for specific antibodies against pCMV-pp65_{495 - 503}/HLA-A2 and design a humanized TCR-like antibody. The affinity of the antibody for the pCMV-pp65_{495 - 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.

In this study, we produced and characterized a TCR-like antibody, 3D7, specific for the pCMV-pp65_{495 - 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.

In conclusion, the TCR-like antibody targeting pCMV-pp65_{495 - 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.