Current landscape of T-cell engagers in early-phase clinical development in solid cancers

  • Front Immunol. 2025 Oct 6:16:1665838. doi: 10.3389/fimmu.2025.1665838.
Andrea Spinazzola  1 Giovanni Maria Iannantuono  1 James L Gulley  2 Elena Giudice  3 Marco Filetti  1 Stefano Sganga  1 Francesca Lo Bianco  1 Charalampos S Floudas  2 Gennaro Daniele  1
Affiliations
  • 1. Phase 1 Unit, Fondazione Policlinico Universitario A. Gemelli, Istituto di ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.
  • 2. Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
  • 3. Division of Gynecologic Oncology, Humanitas San Pio X, Milan, Italy.
Abstract

T-cell engagers (TCEs) are an emerging class of immunotherapeutic agents designed to harness the immune system to target and eliminate Cancer cells. These molecules bridge T lymphocytes with tumor cells, generating an immunologic synapse that leads to potent immune-mediated tumor destruction. Although the clinical activity of TCEs in patients with solid tumors remains insufficient, recent technological advancements have led to the development of several candidates in early-phase clinical trials, with some showing encouraging signs of efficacy. This review examines the current landscape of TCEs in early clinical development for the treatment of solid tumors, describing their mechanism, clinical progress, efficacy, and challenges.

Keywords
T lymphocytes; T-cell engager; early-phase trials; immunotherapy; solid tumors.