Summary of project PR001593
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
| Project ID: | PR001593 |
| Project DOI: | doi: 10.21228/M8SH9M |
| Project Title: | Nano-hijacked myeloid cells potentiate antitumor immunity and radiotherapy for glioblastoma |
| Project Type: | LC-MS/MS |
| Project 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 |
| Email: | jason.miska@northwestern.edu |
| Phone: | 8478678201 |
Summary of all studies in project PR001593
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002467 | Nano-hijacked myeloid cells potentiate antitumor immunity and radiotherapy for glioblastoma | Mus musculus | Northwestern University, Feinberg School of Medicine | MS* | 2023-02-21 | 1 | 6 | Uploaded data (317.4M)* |
