Synthetic High-density Lipoprotein Nanodiscs for Personalized Immunotherapy Against Gliomas

Clin Cancer Res. 2020 Aug 15;26(16):4369-4380. doi: 10.1158/1078-0432.CCR-20-0341. Epub 2020 May 21.


Purpose: Gliomas are brain tumors with dismal prognoses. The standard-of-care treatments for gliomas include surgical resection, radiation, and temozolomide administration; however, they have been ineffective in providing significant increases in median survival. Antigen-specific cancer vaccines and immune checkpoint blockade may provide promising immunotherapeutic approaches for gliomas.

Experimental design: We have developed immunotherapy delivery vehicles based on synthetic high-density lipoprotein (sHDL) loaded with CpG, a Toll-like receptor-9 agonist, and tumor-specific neoantigens to target gliomas and elicit immune-mediated tumor regression.

Results: We demonstrate that vaccination with neoantigen peptide-sHDL/CpG cocktail in combination with anti-PD-L1 immune checkpoint blocker elicits robust neoantigen-specific T-cell responses against GL261 cells and eliminated established orthotopic GL261 glioma in 33% of mice. Mice remained tumor free upon tumor cell rechallenge in the contralateral hemisphere, indicating the development of immunologic memory. Moreover, in a genetically engineered murine model of orthotopic mutant IDH1 (mIDH1) glioma, sHDL vaccination with mIDH1 neoantigen eliminated glioma in 30% of animals and significantly extended the animal survival, demonstrating the versatility of our approach in multiple glioma models.

Conclusions: Overall, our strategy provides a general roadmap for combination immunotherapy against gliomas and other cancer types.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / immunology
  • B7-H1 Antigen / genetics*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / immunology
  • Glioma / pathology
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immunotherapy / methods
  • Lipoproteins, HDL / chemical synthesis
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / pharmacology*
  • Mice
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Precision Medicine
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Temozolomide / administration & dosage
  • Toll-Like Receptor 9 / agonists
  • Toll-Like Receptor 9 / genetics*
  • Toll-Like Receptor 9 / immunology


  • Antigens, Neoplasm
  • B7-H1 Antigen
  • CD274 protein, human
  • Cancer Vaccines
  • Immune Checkpoint Inhibitors
  • Lipoproteins, HDL
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Temozolomide