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Synthetic High-density Lipoprotein Nanodiscs for Personalized Immunotherapy Against Gliomas.


ABSTRACT:

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.

SUBMITTER: Scheetz L 

PROVIDER: S-EPMC7442596 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Synthetic High-density Lipoprotein Nanodiscs for Personalized Immunotherapy Against Gliomas.

Scheetz Lindsay L   Kadiyala Padma P   Sun Xiaoqi X   Son Sejin S   Hassani Najafabadi Alireza A   Aikins Marisa M   Lowenstein Pedro R PR   Schwendeman Anna A   Castro Maria G MG   Moon James J JJ  

Clinical cancer research : an official journal of the American Association for Cancer Research 20200521 16


<h4>Purpose</h4>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.<h4>Experimental design</h4>We have developed immunotherapy delivery vehicles based on synthetic high-  ...[more]

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