Immunostimulant hydrogel for the inhibition of malignant glioma relapse post-resection

Nat Nanotechnol. 2021 May;16(5):538-548. doi: 10.1038/s41565-020-00843-7. Epub 2021 Feb 1.

Abstract

Immunotherapies have revolutionized intervention strategies for many primary cancers, but have not improved the outcomes of glioblastoma multiforme (GBM), which remains one of the most lethal malignant cerebral tumours. Here we present an injectable hydrogel system that stimulates tumoricidal immunity after GBM surgical resection, which mitigates its relapse. The hydrogel comprises a tumour-homing immune nanoregulator, which induces immunogenic cell death and suppression of indoleamine 2,3-dioxygenase-1, and chemotactic CXC chemokine ligand 10, for a sustained T-cell infiltration. When delivered in the resected tumour cavity, the hydrogel system mimics a 'hot' tumour-immunity niche for attacking residual tumour cells and significantly suppresses postoperative GBM recurrence. Our work provides an alternative strategy for conferring effective tumoricidal immunity in GBM patients, which may have a broad impact in the immunotherapy of 'cold' tumours after surgical intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Cells, Cultured
  • Chemokine CXCL10 / administration & dosage
  • Chemokine CXCL10 / therapeutic use*
  • Female
  • Glioblastoma / immunology
  • Glioblastoma / surgery
  • Glioblastoma / therapy*
  • Humans
  • Hydrogels / administration & dosage
  • Hydrogels / therapeutic use*
  • Immunogenic Cell Death / drug effects
  • Immunotherapy
  • Mice
  • Mice, Inbred C57BL
  • Nanomedicine
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control*
  • Rats
  • Rats, Wistar

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents, Immunological
  • Chemokine CXCL10
  • Hydrogels