PROTAC‐Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy
- 1Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University Urumqi China
Abstract
The efficacy of dendritic cell (DC) vaccines in cancer immunotherapy is often limited by weak immunogenicity due to inefficient antigen cross‐presentation (XPT). We previously combined a calcium carbonate (CaCO3) delivery system with a proteolysis‐targeting chimera (PROTAC) to enhance antigen degradation. Along this line, we developed a protein/DNA‐integrated nanoantigen platform (HpOAC) co‐loading CaCO3 with a His‐tagged ovalbumin (O) modified with the von Hippel‐Lindau (VHL) E3 ligase‐recruiting peptide ALAPYIP (HOA) and a eukaryotic plasmid encoding O‐ALAPYIP (pOA). HpOAC promoted DC maturation and migration via Ca2+ release. Mechanistically, HOA provided an immediate antigen source, while pOA enabled sustained expression; both underwent ALAPYIP‐mediated VHL recruitment, enhancing O ubiquitination and proteasomal degradation, thereby amplifying XPT. Consequently, HpOAC‐DCs induced strong OT‐I/OT‐II T cell proliferation in vitro. In vivo, a single immunization with HpOAC‐DCs significantly suppressed tumor growth and elicited durable antigen‐specific T helper type 1 and cytotoxic T lymphocyte responses, outperforming single‐antigen vaccines. Under a two‐dose regimen, its anti‐tumor efficacy was improved compared to non‐PROTAC and in situ antigen vaccines. Thus, we constructed a PROTAC‐enhanced, protein/DNA‐integrated DC vaccine platform that synergizes immediate and sustained antigen supply with Ca2+‐mediated adjuvanticity, offering a highly promising strategy for novel DC vaccine design.
Related
- Rationally Engineered Self-Assembling Protein Nanoparticles for Allergen-Specific Peanut Allergy Immunotherapy
- 860 mRNA-LNP-mediated immunomodulation for precision cancer vaccines and immunotherapy
- Dendritic cell diversity and dysfunction in cancer: implications for immunotherapy and therapeutic targeting
- Dendritic cell-based vaccines for colorectal cancer: Mechanisms, clinical progress and future directions (Review)
- 921 Hybrid lipid nanoparticles enable in situ and ex vivo dendritic cell-based cancer immunotherapy
BibTeX
@article{liu2026protacengineered,
title = {{PROTAC‐Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy}},
author = {Peng Liu and Qiang Chen and Zhe Zhou and Yuekang Xu and Jinyao Li},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.77089},
url = {https://doi.org/10.1002/advs.77089},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PROTAC‐Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy
AU - Peng Liu
AU - Qiang Chen
AU - Zhe Zhou
AU - Yuekang Xu
AU - Jinyao Li
PY - 2026
DA - 2026/08/11
JO - Advanced Science
DO - 10.1002/advs.77089
UR - https://doi.org/10.1002/advs.77089
AB - The efficacy of dendritic cell (DC) vaccines in cancer immunotherapy is often limited by weak immunogenicity due to inefficient antigen cross‐presentation (XPT). We previously combined a calcium carbonate (CaCO3) delivery system with a proteolysis‐targeting chimera (PROTAC) to enhance antigen degradation. Along this line, we developed a protein/DNA‐integrated nanoantigen platform (HpOAC) co‐loading CaCO3 with a His‐tagged ovalbumin (O) modified with the von Hippel‐Lindau (VHL) E3 ligase‐recruiting peptide ALAPYIP (HOA) and a eukaryotic plasmid encoding O‐ALAPYIP (pOA). HpOAC promoted DC maturation and migration via Ca2+ release. Mechanistically, HOA provided an immediate antigen source, while pOA enabled sustained expression; both underwent ALAPYIP‐mediated VHL recruitment, enhancing O ubiquitination and proteasomal degradation, thereby amplifying XPT. Consequently, HpOAC‐DCs induced strong OT‐I/OT‐II T cell proliferation in vitro. In vivo, a single immunization with HpOAC‐DCs significantly suppressed tumor growth and elicited durable antigen‐specific T helper type 1 and cytotoxic T lymphocyte responses, outperforming single‐antigen vaccines. Under a two‐dose regimen, its anti‐tumor efficacy was improved compared to non‐PROTAC and in situ antigen vaccines. Thus, we constructed a PROTAC‐enhanced, protein/DNA‐integrated DC vaccine platform that synergizes immediate and sustained antigen supply with Ca2+‐mediated adjuvanticity, offering a highly promising strategy for novel DC vaccine design.
SN - 2198-3844
ER -