Theme：Targeted Eradication of Malignant Cerebral Tumor

Host：Xinyi Jiang

Time：30th March 2023, 14:00-15:40

Location: Room 110 Med-X Research Institute, Xuhui Campus, SJTU

Glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system, which is highly invasive. Surgical debulking is the first clinical intervention for GBM patient. However, GBM shows invasive growth, has no obvious boundary with normal brain tissue, and cannot be completely removed by surgery. The residual tumor cells after surgery still have strong proliferative capacity, are insensitive to radiotherapy and chemotherapy, and eventually lead to rapid recurrence of brain tumors within a few months. To explore an effective strategy of "specifically" eliminating invasive brain tumors is the key to prevent recurrence after GBM. Immunotherapy has brought unprecedented changes and hopes for cancer treatment. However, there is no successful immunotherapy program for GBM at present. Through the analysis of clinical samples of GBM patients, we confirmed that the expression levels of multiple biomarkers such as IDH1, IDO1 and CD133 in malignant brain tumor tissues were significantly increased, and were negatively correlated with the survival of patients. In view of this, we have constructed two nanocarrier-hydrogel superstructure drug delivery systems that can reshape the tumor immune microenvironment in situ to curb the recurrence of GBM after surgery: (i) induce immunogenic death, activate and recruit T lymphocytes, silence IDO1 to relieve the function and efficiency of Treg cell immune "brake", cascade to reshape the tumor killing immune microenvironment, and curb the recurrence of GBM after surgery; (ii) Generate CAR macrophages around the tumor cavity in vivo that can target the removal of glioma stem cells (GSCs), activate the adaptive immune system by its antigen presentation, remove residual GSCs after surgery, and avoid GBM tumor recurrence. Intracavity drug delivery offers a convenient and effective approach that can be seamlessly integrated with clinical surgical debulking without the need for additional surgery.