Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma

Abstract

In situ fibrin gel promotes the survival and the biodistribution of CAR-T cells, eliminating residual GBM cells after surgery.

Recent advances in biomaterial-boosted adoptive cell therapy

“…Ogunnaike et al constructed a fibrin gel for regional delivery of CAR-T cells by enzymatically cross-linking human fibrinogen and thrombin. 168 In a murine model of glioblastoma, the fibrin gel was rapidly formed in situ by mixing the fibrin solution loading CD19 CAR-T cells and thrombin solution into the tumor resection cavity. Subsequently, the sustained release of the implanted CAR-T cells into tumor residues led to the complete suppression of tumor recurrence compared with local delivery of free CAR-T cells.…”

Sprayable hydrogel for biomedical applications

“…102,104 Moreover, the structure of the fibrin-based hydrogel can be straightforwardly regulated by changing the concentration of thrombin and fibrinogen in the hydrogel precursors. Based on these characteristics, fibrin-based hydrogels are widely applied in bone tissue engineering, 102 neural tissue injury, 105 wound healing, 106 superficial cancer therapies 24,107,108 and so on.…”

“…102,104 Moreover, the structure of the fibrin-based hydrogel can be straightforwardly regulated by changing the concentration of thrombin and fibrinogen in the hydrogel precursors. Based on these characteristics, fibrinbased hydrogels are widely applied in bone tissue engineering, 102 neural tissue injury, 105 wound healing, 106 superficial cancer therapies 24,107,108 and so on. Fibrin can stimulate wound healing immediately by modulating cell behaviour and transforming into a delivery hydrogel system through fine-tuning for the extended release of therapeutic agents, growth factors, cells and so on.…”

Recent advances in biomaterial-assisted cell therapy

“…Besides, Ogunnaike et al proposed fibrin gels loaded with CAR-T cells to achieve slow release of the effector cells to the target region and promote higher antitumor activity than directly injecting CAR-T cells to the site. 70 A porous gel generated from human fibrinogen through thrombin-mediated enzymatic polymerization was designed to encapsulate T cells, which could gradually release the effector cells at the tumor resection cavity after in situ gel formation. The CAR-T cells that were deposited by the fibrin gel demonstrated effective antitumor activity in glioblastoma resection mouse models.…”