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 |
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Sample Preparation:
Sampleprep ID: | SP002563 |
Sampleprep Summary: | Isolated TAMC and CD8+ T cells samples were dried using a SpeedVac. Acetonitrile (50%) was added to the tube for reconstitution following overtaxing for 30 s. Sample solution was then centrifuged for 15 min at 20,000g and 4°C. Supernatant was collected for LC-MS analysis. The mobile phase A contained 95% water/5% acetonitrile (v/v), 20 mM ammonium hydroxide, and 20 mM ammonium acetate (pH 9.0); phase B was 100% acetonitrile. The gradient was performed as follows: 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 with a flow rate of 400 μl/min. The capillary of the electrospray ionization source was set to 275°C, with sheath gas at 45 arbitrary units, auxiliary gas at 5 arbitrary units, and the spray voltage at 4.0 kV. In positive/negative polarity switching mode, a mass/charge ratio (m/z) scan range from 70 to 850 was chosen and MS1 data were collected at a resolution of 70,000. The automatic gain control target was set at 1 × 106, and the maximum injection time was 200 ms. The top five precursor ions were subsequently fragmented, in a data-dependent manner, using the higher-energy collisional dissociation cell set to 30% normalized collision energy in MS2 at a resolution power of 17,500. |