Recently, Professor Lingyi Kong and Associate Researcher Chao Zhang from the School of Traditional Chinese Pharmacy published a research paper entitled “Enhancing immunogenicity and release of in situ-generated tumor vesicles for autologous vaccines” in the Journal of Controlled Release. Dr. Jinhu Chen (Ph.D. student, class of 2021) and Caili Zhao (M.S. student, class of 2020) are the co-first authors of the paper. Prof. Lingyi Kong, Associate Researcher Chao Zhang and Prof. Jianguang Luo are the corresponding authors. China Pharmaceutical University is the sole correspondent.
Cancer vaccines, as an important direction of tumor immunotherapy, show great potential in personalized treatment, but their clinical translation still faces key bottlenecks such as low antigen delivery efficiency and immunosuppressive microenvironment. To address this challenge, the research team innovatively proposed a tumor in situ vaccine strategy based on the active ingredients of traditional Chinese medicine, and realized a therapeutic breakthrough through the synergistic effect of Epimedium hypoglutinoside II and Andrographis paniculatum lactone in dispelling wind and detoxifying toxins.
The study found for the first time that the two active ingredients of Chinese medicine can synergistically induce necrotic apoptosis and trigger immunogenic death of tumor cells, and at the same time dually regulate the loading of protein cargoes in tumor-derived extracellular vesicles (TEVs) through the STAT3 signaling pathway. Experiments confirmed that this strategy significantly reduced the loading of immune checkpoint proteins, such as PD-L1 and CD47, in TEVs, while promoting the enrichment of damage-associated molecular patterns (DAMPs), and increased the release efficiency of immunopotentiated TEVs to 56.44%. Animal experiments showed that the combined glyco-immune checkpoint inhibitors could significantly increase the infiltration of CD44+CD8+ T cells in the tumor microenvironment, and successfully transformed the “cold tumors” into “hot tumors”, which prolonged the survival period of mice with osteosarcoma and breast cancer by more than 1-fold.
This study not only reveals for the first time the synergistic regulatory mechanism of active ingredients of traditional Chinese medicine on tumor vesicles, but also provides an innovative solution to break through the immunotherapy tolerance of solid tumors. Based on the unique advantages of the active ingredients of TCM, this strategy has demonstrated significant clinical translational potential while maintaining highly effective anti-tumor activity.
Schematic diagram of the mechanism of synergistic action of Icariin II and Andrographolide
This work was supported by the National Natural Science Foundation of China (82474063, 82274073, 81872986), the National Key Research and Development Program of China (2024ZD0520400), the Central Universities Scientific Research Funds (2632024TD08), the “Double First-class” Discipline Construction Project (CPU2022QZ28), and the National Key Laboratory of Multi-targeted Natural Medicines. Open Project (SKLNMKF202404).
Link to the paper: https://doi.org/10.1016/j.jconrel.2025.113614
