Synthetic high-density lipoprotein nanodiscs for personalized immunotherapy against gliomas
2020
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 therapeutic approaches for gliomas.
Experimental Design: Here, 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 (NeoAgs) to target gliomas and elicit immune-mediated tumor regression.
Results: We demonstrate that vaccination with NeoAg peptide-sHDL/CpG cocktail in combination with anti-PDL1 immune checkpoint blocker elicits robust NeoAg-specific T cell responses against GL261 cells and eliminated established orthotopic GL261 glioma in 33% of mice. Mice remained tumor free upon tumor cell re-challenge in the contralateral hemisphere, indicating the development of immunological memory. Moreover, in a genetically engineered murine model of orthotopic mutant IDH1 (mIDH1) glioma, sHDL vaccination with mutant IDH1 NeoAg 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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
49
References
20
Citations
NaN
KQI