Summary of project PR001593

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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

Summary of all studies in project PR001593

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : 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)*