An inhalable microbe-oncolytic virus consortium for lung cancer treatment

Oncolytic viruses (OVs) represent a promising cancer therapy due to their selective cytotoxicity, yet clinical success in lung cancer is hindered by biological barriers and immunosuppressive microenvironments. To address these barriers, an inhalable microbe-OVs consortium is developed by conjugating tumor-responsive PEGylated adenoviruses (Ads) to motile algae (Synechococcus WH8102) via click chemistry. Driven by algal motility, the consortium penetrates respiratory mucus and epithelial barriers to reach lung tumor sites. Intratumoral calcium ion deprivation by the algae disrupts cellular tight junctions and facilitates deep penetration into solid tumors, thereby potentiating Ads-mediated immunogenic cell death (ICD) and boosting microbial and viral co-activated antitumor immunity. Inhalation administration demonstrates robust antitumor effectiveness in murine lung tumor. This inhalable microbe-OV strategy provides a promising scheme for clinical oncolytic microorganism biotherapeutics.