REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicAdvancements in Immunotherapy Biologics for Cancer and Infectious DiseasesView all 4 articles
Synthetic Biology approaches to enhance cancer immune responses
Provisionally accepted
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China
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Synthetic biology is being widely applied in tumor therapy, ranging from attenuating microbial toxicity to constructing synthetic gene circuits and developing CAR-T cells, all of which are reshaping the landscape of cancer immunotherapy. In this review, we summarize recent advances in microbial-based therapeutics that leverage bacteria's natural tropism for hypoxic tumor regions to deliver immunomodulatory payloads with high spatial precision. Parallel progress in CAR-T cell engineering has led to the development of armored and logic-gated constructs designed to overcome challenges such as antigen heterogeneity, the immunosuppressive tumor microenvironment, and T cell exhaustion. Synthetic biology further integrates these platforms via programmable genetic circuits capable of performing Boolean logic operations, ensuring therapeutic activation only in the presence of tumor-specific biomarkers. While this convergence offers the unprecedented precision, safety, and potency in reprogramming anti-tumor immunity, the clinical translation of these complex systems faces significant hurdles. Despite challenges in clinical translation-including safety concerns, immune clearance, and manufacturing complexity-the field is advancing toward multifunctional "smart" therapies, synergistic microbial-cell combinations, and personalized treatment strategies. Together, these innovations are defining a new generation of precision-engineered immunotherapies with the potential to transform the treatment of refractory malignancies.
Keywords: synthetic biology1, engineered bacteria2, CAR-T cells3, synthetic gene circuits4, cancer immunotherapy5
Received: 03 Sep 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Liu, Zhong, Tu and Jin. 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: Meiling Jin, ml.jin@siat.ac.cn
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