Drug-loaded lipid nanoparticles targeting tumor-associated myeloid cells for glioma

INDICATION: Brain cancer

Targeting immunosuppressive tumor-associated myeloid cells (TAMCs) with drug-loaded anti-PD-L1 lipid nanoparticles could treat glioma, an indication in which TAMCs contribute up to 50% of the tumor mass. The nanoparticles, loaded with a small hydrophobic drug, have phospholipid bilayers of cardiolipin, cholesterol and phosphatidylcholine conjugated to an anti-PD-L1 mAb. In cultured immune infiltrates isolated from glioma tumors in mice, nanoparticles loaded with the CDK1 inhibitor dinaciclib eliminated TAMCs without toxicity to tumor-infiltrating lymphocytes. In mice modeling aggressive glioma, the dinaciclib-loaded nanoparticles extended median survival from 20 days to 28.5 days. Also in the model, dinaciclib-loaded nanoparticles plus radiation therapy extended median survival from 17 days to 32 days, while monotherapy with either treatment led to a 22.5 day median survival. Next steps include testing the dinaciclib-loaded nanoparticles in clinical trials and seeking partners to scale up manufacturing...