Self-assembling paclitaxel-mediated stimulation of tumor-associated macrophages for postoperative treatment of glioblastoma.
Feihu WangQian HuangHao SuMingjiao SunZeyu WangZiqi ChenMengzhen ZhengRami W ChakrounMaya K MonroeDaiqing ChenZongyuan WangNoah GorelickRiccardo SerraHan WangYun GuanJung Soo SukBetty TylerHenry BremJustin HanesHonggang CuiPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic "don't eat me" signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects.
Keyphrases
- drug delivery
- immune response
- end stage renal disease
- hyaluronic acid
- peritoneal dialysis
- newly diagnosed
- single cell
- adipose tissue
- stem cells
- prognostic factors
- bone marrow
- cell therapy
- small molecule
- tissue engineering
- wound healing
- combination therapy
- dendritic cells
- mesenchymal stem cells
- replacement therapy
- quantum dots
- blood brain barrier