Intrinsic PD‐L1 Degradation Induced by a Novel Self‐Assembling Hexapeptide for Enhanced Cancer Immunotherapy DOI Creative Commons
Hongxia Zhang, Ming Ji, Yamei Wang

и другие.

Advanced Science, Год журнала: 2024, Номер 12(2)

Опубликована: Ноя. 12, 2024

Abstract Programmed death‐ligand 1 (PD‐L1) is a critical immune checkpoint protein that facilitates tumor evasion. While antibody‐based PD‐1/PD‐L1 inhibitors have shown promise, their limitations necessitate the development of alternative therapeutic strategies. This work addresses these challenges by developing hexapeptide, KFM (Lys‐Phe‐Met‐Phe‐Met‐Lys), capable both directly downregulating PD‐L1 and self‐assembling into ROS‐responsive supramolecular hydrogel. dual functionality allows Gel to function as localized drug delivery system inhibitor. Loading hydrogel with mitoxantrone (MTX) metformin (MET) further enhances effect combining chemotherapy downregulation. In vitro in vivo studies demonstrate significant growth inhibition, increased CD8+ T cell infiltration, reduced intratumoral expression following peritumoral administration. Mechanistically, promotes degradation via ubiquitin‐dependent pathway. “carrier‐free” expands role hydrogels beyond passive carriers active immunotherapeutic agents, offering promising new strategy for cancer therapy.

Язык: Английский

Intrinsic PD‐L1 Degradation Induced by a Novel Self‐Assembling Hexapeptide for Enhanced Cancer Immunotherapy DOI Creative Commons
Hongxia Zhang, Ming Ji, Yamei Wang

и другие.

Advanced Science, Год журнала: 2024, Номер 12(2)

Опубликована: Ноя. 12, 2024

Abstract Programmed death‐ligand 1 (PD‐L1) is a critical immune checkpoint protein that facilitates tumor evasion. While antibody‐based PD‐1/PD‐L1 inhibitors have shown promise, their limitations necessitate the development of alternative therapeutic strategies. This work addresses these challenges by developing hexapeptide, KFM (Lys‐Phe‐Met‐Phe‐Met‐Lys), capable both directly downregulating PD‐L1 and self‐assembling into ROS‐responsive supramolecular hydrogel. dual functionality allows Gel to function as localized drug delivery system inhibitor. Loading hydrogel with mitoxantrone (MTX) metformin (MET) further enhances effect combining chemotherapy downregulation. In vitro in vivo studies demonstrate significant growth inhibition, increased CD8+ T cell infiltration, reduced intratumoral expression following peritumoral administration. Mechanistically, promotes degradation via ubiquitin‐dependent pathway. “carrier‐free” expands role hydrogels beyond passive carriers active immunotherapeutic agents, offering promising new strategy for cancer therapy.

Язык: Английский

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