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Peer-reviewedCC BY 4.0Frontiers in Immunology

Bioengineering strategies to enhance BCG immunotherapy against bladder cancer

  • Senhao Li1
  • Haige Chen1
  • Bing Feng2
  1. 1Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
  2. 2Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Functional Nucleic Acids for Basic and Clinical Application, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
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Abstract

Bacillus Calmette–Guérin (BCG) remains the frontline immunotherapy for non–muscle-invasive bladder cancer (NMIBC), yet recurrence and non-response occur in over half of patients, highlighting the need for improved therapeutic strategies. Recent advances in bioengineering including genetic modification, synthetic biology, biomaterials, and delivery systems are expanding BCG from a traditional vaccine into a more versatile immunotherapeutic platform. In this review, we summarize the mechanisms of BCG-induced antitumor immunity and discuss current bioengineering strategies aimed at enhancing tumor interaction, innate immune activation, and modulation of the tumor immune microenvironment (TIME). We further highlight emerging approaches in delivery system design to improve intravesical retention and therapeutic efficacy. In addition, we discuss evolving perspectives on immune regulation in BCG therapy, including the potential contribution of type 2 immunity alongside canonical type 1 responses, as well as the role of trained immunity in sustaining antitumor effects. Finally, we outline key challenges for clinical translation and future directions toward more rational and precise BCG-based immunotherapy.

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Cite

BibTeXRIS
BibTeX
@article{li2026bioengineering,
  title = {{Bioengineering strategies to enhance BCG immunotherapy against bladder cancer}},
  author = {Senhao Li and Haige Chen and Bing Feng},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1888889},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1888889/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Bioengineering strategies to enhance BCG immunotherapy against bladder cancer
AU  - Senhao Li
AU  - Haige Chen
AU  - Bing Feng
PY  - 2026
DA  - 2026/10/05
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1888889
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1888889/full
AB  - Bacillus Calmette–Guérin (BCG) remains the frontline immunotherapy for non–muscle-invasive bladder cancer (NMIBC), yet recurrence and non-response occur in over half of patients, highlighting the need for improved therapeutic strategies. Recent advances in bioengineering including genetic modification, synthetic biology, biomaterials, and delivery systems are expanding BCG from a traditional vaccine into a more versatile immunotherapeutic platform. In this review, we summarize the mechanisms of BCG-induced antitumor immunity and discuss current bioengineering strategies aimed at enhancing tumor interaction, innate immune activation, and modulation of the tumor immune microenvironment (TIME). We further highlight emerging approaches in delivery system design to improve intravesical retention and therapeutic efficacy. In addition, we discuss evolving perspectives on immune regulation in BCG therapy, including the potential contribution of type 2 immunity alongside canonical type 1 responses, as well as the role of trained immunity in sustaining antitumor effects. Finally, we outline key challenges for clinical translation and future directions toward more rational and precise BCG-based immunotherapy.
SN  - 1664-3224
ER  -