AccScience Publishing / OR / Online First / DOI: 10.36922/OR025500039
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COMMENTARY

A modular protein approach to next-generation in situ cancer vaccines: A commentary

Mai Zhang1 ,  Jing Tian2 ,  Xuemei Fu1 ,  Dingkang Liu1,2*
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1 Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
2 Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, China
OR, 025500039 https://doi.org/10.36922/OR025500039
Received: 9 December 2025 | Revised: 6 January 2026 | Accepted: 12 January 2026 | Published online: 5 February 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Cancer immunotherapy has revolutionized in situ vaccination approaches that leverage endogenous tumor antigens to initiate immune responses. This commentary examines the protease-activated PSTAGylated in situ tumor vaccine (PPTV), a modular metalloprotein platform engineered for precise co-delivery of mitochondria-disrupting peptides and manganese ions. Utilizing ferritin as a biodegradable chassis, PPTV achieves tumor-specific activation through matrix metalloproteinase 14 cleavage, inducing immunogenic cell death and activating the stimulator of interferon genes pathway. Preclinical models demonstrate potent antitumor immunity, with combination therapy eradicating established tumors. The integration of patient-derived organoids is proposed to personalize immunotherapy, highlighting the translational potential of biomaterial-based vaccines for overcoming present limitations in cancer treatment.

Keywords
Cancer immunotherapy
Metalloprotein
Immunogenic cell death
Stimulator of interferon genes pathway
Patient-derived organoids
Funding
This research was supported by the National Natural Science Foundation of China (No. 82304368).
Conflict of interest
The authors declare that they have no competing interests.
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Organoid Research, Electronic ISSN: 3082-8503 Published by AccScience Publishing
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