Tumor cells escape immune eradication through multiple mechanisms including loss of antigenicity and local suppression of effector lymphocytes. In order to counteract these obstacles, we aimed to direct the unique cytomegalovirus-specific immune surveillance against tumor cells. We developed a novel generation of fusion proteins composed of a tumor antigen-specific full immunoglobulin connected to a single major histocompatibility class I complex bearing a covalently linked virus-derived peptide (pMHCI-IgG). Here, we show that tumor antigen expressing cancer cells decorated with pMHCI-IgGs containing a HLA-A*0201 molecule associated with a cytomegalovirus-derived peptide are specifically eliminated through engagement of antigen-specific CD8+ T cells isolated from peripheral blood mononuclear cell preparations of cytomegalovirus-infected humans. These CD8+ T cells act without additional expansion, pre-activation or provision of co-stimulatory signals. Elimination of tumor cells is induced at similar concentrations and with similar time kinetics as those seen with bispecific T cell engagers (BiTEs). However, while BiTE-like reagents indiscriminately activate T cells through binding to the T cell receptor complex, pMHCI-IgGs selectively engage antigen-specific, constantly renewable, differentiated effector cytotoxic T lymphocytes to tumor cells, thereby representing a novel class of anti-cancer immunotherapeutics with potentially improved safety and efficacy profiles.
- Received February 3, 2015.
- Accepted February 7, 2015.
- Copyright © 2015, American Association for Cancer Research.