A tri-specific antibody engages T and myeloid cells to augment anti-tumor immunity

Immunologically inert tumors often resist immune checkpoint inhibitors due to a scarcity of tumor-specific T cells and the immunosuppressive microenvironment, despite pronounced and functional bystander T cell infiltration. Here, we develop a novel tri-specific T cell engager (Tri-TCE) designed in a unique format to redirect T cells while mitigating immunosuppression. Our comprehensive studies utilizing co-culture systems, patient-derived tumor suspensions (PDTSs), patient-derived tumor fragments (PDTFs), and humanized mouse tumor models, demonstrate that Tri-TCE effectively activates T cells and induces tumor cell lysis. Human PBMCs were successfully reconstituted into engineered immunodeficient mice, followed by SKOV3 tumor implantation. Mice received two doses of control IgG, BiTE or Tri-TCE during the treatment course. We further conducted RNA sequencing of the isolated tumor tissues at the end of experiments.