Summary of Study ST002467

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001593. The data can be accessed directly via it's Project DOI: 10.21228/M8SH9M This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002467
Study TitleNano-hijacked myeloid cells potentiate antitumor immunity and radiotherapy for glioblastoma
Study TypeIR versus IR + LNP
Study SummaryAbstract: Radiation therapy is a key component of the standard of care for glioblastoma (GBM). Although this treatment is known to trigger pro-inflammatory immune responses, it also results in several immune resistance mechanisms such as the upregulation of CD47 by tumors leading to avoidance of phagocytosis and the overexpression of PD-L1 in tumor-associated myeloid cells (TAMCs). Leveraging these RT-elicited processes, we generated a bispecific-lipid nanoparticle (B-LNP) that engaged TAMCs to glioma cells via anti-CD47/PD-L1 dual-ligation. We show that B-LNP blocked these two vital immune checkpoint molecules and promoted the phagocytic activity of TAMCs. In order to boost subsequent T cell recruitment and antitumor activity after tumor engulfment, the B-LNP was encapsulated with diABZI, a non-nucleotidyl agonist for stimulator of interferon genes (STING). In vivo treatment with the diABZI-loaded B-LNP induced a transcriptomic and metabolic switch in TAMCs, transforming them into potent antitumor effector cells, which induced T cell infiltration and activation of in the brain tumors. In preclinical murine glioma models, B-LNP therapy significantly potentiated the antitumor effects of radiotherapy, promoted brain tumor regression, and induced immunological memory against gliomas. The nano37 therapy was efficacious through both intra-tumoral and systemic delivery routes. In summary, our study shows a unique nanotechnology-based approach that hijacks multiple immune checkpoints to boost potent and long-lasting antitumor immunity against GBM.
Institute
Northwestern University, Feinberg School of Medicine
DepartmentNeurological Surgery
LaboratoryJason Miska
Last NameMiska
First NameJason
Address676 N St. Clair
Emailjason.miska@northwestern.edu
Phone8478678201
Submit Date2023-02-06
Num Groups2
Total Subjects6
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-02-21
Release Version1
Jason Miska Jason Miska
https://dx.doi.org/10.21228/M8SH9M
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Subject:

Subject ID:SU002557
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
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