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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST002467 |
| Study Title | Nano-hijacked myeloid cells potentiate antitumor immunity and radiotherapy for glioblastoma |
| Study Type | IR versus IR + LNP |
| Study Summary | Abstract: 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 |
| Department | Neurological Surgery |
| Laboratory | Jason Miska |
| Last Name | Miska |
| First Name | Jason |
| Address | 676 N St. Clair |
| jason.miska@northwestern.edu | |
| Phone | 8478678201 |
| Submit Date | 2023-02-06 |
| Num Groups | 2 |
| Total Subjects | 6 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-02-21 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004023 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Q Exactive™ Plus Hybrid Quadrupole-Orbitrap™ Mass Spectrometer |
| Column | Water's Xbridge amide (100 x 3mm, 3.5 um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive Plus Orbitrap |
| Ion Mode | UNSPECIFIED |
| Units | Normalized peak area |
Chromatography:
| Chromatography ID: | CH002973 |
| Chromatography Summary: | Samples were analyzed by high-performance LC (HPLC) and high-resolution MS and MS/MS (HPLC-MS/MS). The system consists of Thermo Q Exactive with an electrospray source and an UltiMate3000 (Thermo Fisher Scientific) series HPLC consisting of a binary pump, degasser, and autosampler outfitted with an XBridge Amide column (Waters; dimensions of 4.6 mm by 100 mm and a 3.5-μm particle size). |
| Instrument Name: | Q Exactive™ Plus Hybrid Quadrupole-Orbitrap™ Mass Spectrometer |
| Column Name: | Water's Xbridge amide (100 x 3mm, 3.5 um) |
| Column Temperature: | 275 |
| Flow Gradient: | 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% A; 16 min, 62% A; 16.1 to 18 min, 75% A; and 18 to 25 min, 15% A |
| Flow Rate: | 400 μl/min |
| Solvent A: | 95% water/5% acetonitrile; 20 mM ammonium hydroxide; 20 mM ammonium acetate (pH 9.0) |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | HILIC |
