Cancer

Mouse studies suggest polymer vesicles loaded with the STING agonist cGAMP could help treat melanoma. The vesicles consist of cGAMP encapsulated in a polyethylene glycol (PEG)-based polymer membrane based on pH-sensitive, cationic diethylamino-based groups and hydrophobic butylmethacrylate groups to allow for intracellular release and endosomal escape. In a mouse model of melanoma, intratumoral injection with the cGAMP-loaded polymer vesicles decreased tumor growth and increased survival compared with free cGAMP and/or empty vesicles, and prevented tumor recurrence after secondary challenge with melanoma cells in five of seven treated animals. Also in the model, IV injection of the cGAMP-loaded vesicles plus anti-PD-1 and anti-CTLA-4 mAbs decreased tumor growth and increased survival compared with the cGAMP-loaded vesicles alone or the mAb combination. In a mouse model of melanoma harboring tumors on each flank, injection into one tumor of the cGAMP-loaded vesicles alone or with the two-mAb combination decreased growth of both tumors compared with the mAb combination alone. Next steps include PK/PD studies of the cGAMP-loaded vesicles.

Aduro Biotech Inc. and Novartis AG have ADU-S100, a synthetic cyclic dinucleotide that activates the STING pathway, in Phase I testing for lymphoma and solid tumors...