Antigen-Targeting Inserted Nanomicelles Guide Pre-Existing Immunity to Kill Head and Neck Cancer

  • Adv Sci (Weinh). 2025 May;12(18):e2410629. doi: 10.1002/advs.202410629.
Lizhuo Zhang  1  2  3 ,  Qingqing Feng  4 ,  Chuanming Zheng  1  2  3 ,  Yuanqiang Li  5 ,  Xinyang Ge  6 ,  Tiefeng Jin  7 ,  Gaofeng Hu  5 ,  Zhuo Tan  1  2  3 ,  Jiafeng Wang  1  2  3  8 ,  Jiajie Xu  1  2  3 ,  Liehao Jiang  1  2  3 ,  Dan Wang  1 ,  Zhangguo Ying  5 ,  Xiao Zhao  9 ,  Keman Cheng  9 ,  Qinglin Li  5 ,  Minghua Ge  1  2  3
Affiliations
  • 1. Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, China.
  • 2. Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Hangzhou, 310014, China.
  • 3. Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou, 310014, China.
  • 4. Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310006, China.
  • 5. Zhejiang Cancer Hospital, Hangzhou, 310005, China.
  • 6. Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
  • 7. Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, SAR, 999078, China.
  • 8. Department of Thyroid and Breast Surgery, Zhejiang Provincial People's Hospital Bijie Hospital, Bijie, 551700, China.
  • 9. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.
PMID: 40091501 DOI: 10.1002/advs.202410629
Abstract

A significant challenge in Cancer therapy is the identification of suitable targets that are specifically and uniformly expressed across heterogeneous tumors. The efficacy of pre-existing Antiviral immunity in tumor treatment is limited by the absence of corresponding targets. This study develops a novel platform of antigen-targeted inserted nanomicelles, preS1 (an antigen of hepatitis B virus)-pHLIP nanomicelles, in which tumor-targeting nanomicelles release antigens that label tumor tissue for pre-existing immunity-mediated lysis in situ. In animal models of head and neck cancers, including head and neck squamous cell carcinoma and anaplastic thyroid Cancer, preS1-pHLIP nanomicelles effectively inhibited tumor growth, recurrence, and metastasis in Animals pre-immunized with preS1. This therapeutic effect is associated with an increase in the proportion of preS1-specific B cells and activated tumor-specific T cells within the tumor microenvironment. Overall, this work has engineered a nanomicelle that can disguise tumor cells as viruses and achieve tumor killing through the pre-existing Antiviral immune response. This strategy presents a novel approach for treating tumors with ambiguous therapeutic target profiles.

Keywords
cancer immunotherapy; head and neck cancer; nanomicelle; preS1; reprogramming of “anti‐viral immunity” into “anti‐tumor immunity”.
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