REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1665838
Current Landscape of T-Cell Engagers in Early-Phase Clinical Development in Solid Cancers
Provisionally accepted
Andrea Spinazzola1
Giovanni Maria Iannantuono1
James L. Gulley2Elena Giudice3
Marco Filetti1Stefano Sganga1Francesca Lo Bianco1
Charalampos Floudas2
Gennaro Daniele1*- 1Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- 2National Cancer Institute Center for Cancer Research, Bethesda, United States
- 3IRCCS Humanitas Research Hospital, Rozzano, Italy
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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: solid tumors, t-cell engager, Immunotherapy, early-phase trials, T lymphocytes
Received: 14 Jul 2025; Accepted: 16 Sep 2025.
Copyright: © 2025 Spinazzola, Iannantuono, Gulley, Giudice, Filetti, Sganga, Lo Bianco, Floudas and Daniele. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gennaro Daniele, gennaro.daniele@policlinicogemelli.it
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.