REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1680410
This article is part of the Research TopicExploring T Cell Driven Immunotherapies: From CAR T and TILs to T Cell EngagersView all 3 articles
Multiplex engineering and multifunction T cells for precise and effective immunotherapies
Provisionally accepted
- 1Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Canada
- 2Universite de Montreal, Montreal, Canada
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Adoptive T cell transfer has emerged as a pillar of modern cancer immunotherapy. Propelled by viral and non-viral-based technologies, such as CRISPR-Cas9, genetic engineering offers novel opportunities for both emerging cellular therapies and the improvement of more established approaches such as chimeric antigen receptor (CAR) modified T cells. First-generation genetically modified T-cell therapeutics remain limited by the intrinsic constraints imposed by T-cell biology, such as T-cell exhaustion, poor trafficking into hostile tumor beds, toxicity, and challenges associated with tumor antigenic escape. Several of such limitations can be addressed by further engineering, expanding significantly the potential of cell therapy. This review focuses on the promise of using currently available cellular engineering technologies to genetically engineer single T cells at multiple different loci and/or confer several novel functions to circumvent the shortcomings of adoptive immunotherapy to treat cancer. Various methodologies and rationales for the design of these advanced engineered cellular products are described, along with emerging clinical data supporting the use of multiplex-engineered T cells. The limitations of advanced cell engineering and the remaining gaps that need to be filled to optimize the efficacy of adoptive T-cell immunotherapies are also discussed.
Keywords: Adoptive immunotherapy, Genetic Engineering, cancer immunotherapy, T cells, CRISPR-Cas9, Chimeric Antigen Receptor
Received: 05 Aug 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Jafarzadeh, Smaani and Delisle. 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: Jean-Sébastien Delisle, js.delisle@umontreal.ca
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