# Novel nano-vaccine technology for inducing immunity against gliomas

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $501,930

## Abstract

Abstract
Despite the success of immune checkpoint blockade in cancer therapy, their use has benefited only a subset of
cancer patients. The multiple mechanisms utilized by tumors to inhibit an anti-tumor immune response have
impeded their widespread use as monotherapies, and this is particularly true for gliomas. Therefore, there exists
a critical need for new, complementary strategies for achieving powerful and durable immune responses against
gliomas. In particular, mutant isocitrate-dehydrogenase-1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas.
We have developed a fully immune competent murine mIDH1 model by incorporating genetic lesions
encountered in the human disease into the genomic DNA of neural progenitor cells using Sleeping Beauty
Transposase and shown that these intracranial tumors exhibit the hallmarks of human mIDH1 glioma. Our long-
term research goal is to develop novel strategies that can achieve immune stimulation with potent anti-mIDH1
glioma immunity. Our main objectives in this application are to engineer a powerful and safe platform vaccine
technology for inducing robust, durable anti-tumor memory T-cell responses against mIDH1 gliomas. To this
end, we have developed a new vaccine technology based on synthetic high-density lipoprotein (sHDL)
nanodiscs. We have shown that sHDL nanodiscs efficiently deliver antigens and adjuvant molecules to antigen-
presenting cells and achieve strong T-cell responses with robust cytotoxic potential. Here, we propose to
evaluate the therapeutic efficacy of sHDL nanoparticles in genetically engineered murine glioma models and
transplantable intracranial gliomas. Specifically, we propose to (1) optimize our nanotechnology for improved
mIDH1 Ag delivery and elicit durable memory T-cell responses against mIDH1 glioma (Aim 1); (2) evaluate their
efficacy to eradicate mIDH1 gliomas using neurospheres derived from the mIDH1 genetically engineered glioma
model (GEM) implanted into immunocompetent mice (Aim 2); (3) test the hypothesis that combining nanodisc
vaccination with standard of care (radiation) and anti-PD-L1 immune checkpoint blockade will elicit robust anti-
mIDH1 glioma immunity with long-term immunological memory in mIDH1 GEMs. These studies will shed new
light on nano-vaccine delivery platforms for precision immunotherapy. More broadly, the work proposed will
address current technical limitations in vaccine technologies and potentially lead to a new treatment option for
mIDH1 glioma patients.

## Key facts

- **NIH application ID:** 10241830
- **Project number:** 1R01NS122536-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Maria G Castro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $501,930
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241830

## Citation

> US National Institutes of Health, RePORTER application 10241830, Novel nano-vaccine technology for inducing immunity against gliomas (1R01NS122536-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241830. Licensed CC0.

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