2. Academic Validation
  3. In situ therapeutic vaccines for leukemia by chemo-nanoadjuvant therapy

In situ therapeutic vaccines for leukemia by chemo-nanoadjuvant therapy

  • J Control Release. 2025 Jul 10:383:113851. doi: 10.1016/j.jconrel.2025.113851.
Peng Zhang 1,  Guanhong Cui 1,  Tanzhen Wang 2,  Xiaofei Zhao 1,  Xinyue Wang 3,  Ruonan Ye 1,  Tianhui Liu 4,  Yiran Zheng 5,  Zhiyuan Zhong 6
Affiliations

Affiliations

  • 1 Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China.
  • 2 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215000, PR China.
  • 3 College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China.
  • 4 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215000, PR China. Electronic address: liutianhui@suda.edu.cn.
  • 5 College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China. Electronic address: yrzheng@suda.edu.cn.
  • 6 Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China; College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China. Electronic address: zyzhong@suda.edu.cn.
PMID: 40389164 DOI: 10.1016/j.jconrel.2025.113851
Abstract

Therapeutic vaccines introduce a potentially ultimate cure for cancers including leukemia. The personalized vaccines relying on neoantigens though exhibiting clinical benefits are afflicted by long and delicate manufacture procedure, high cost, and possibly incomplete coverage of heterogeneous tumor cells. Here, we report a facile strategy to generate potent in situ therapeutic vaccines, which effectively eliminate leukemia and induce long-term anti-leukemia immunity, by homoharringtonine-nano-dual-adjuvant (HHT-NDA) therapy. HHT effectively kills leukemia cells and generates abundant tumor antigens via inducing immunogenic cell death. NDAs cooperatively promote the maturation and antigen-presentation of dendritic cells by activating both nucleotide-binding oligomerization domain-containing protein 2 and Toll-like Receptor 9. The HHT-NDA treatment of murine MLL-AF9 acute myeloid leukemia model leads to 57-71 % complete regression and 100 % protection from rechallenge, in accordance with expansion of memory CD8+ T cells. This standard-of-care chemotherapy in tandem with nano-dual-adjuvant offers a novel strategy to generate in situ therapeutic vaccines for leukemia.

Keywords

Blood cancer; Cancer vaccines; Immunogenic cell death; Nanoadjuvants; Polymersomes.

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