An inhalable microbe-oncolytic virus consortium for lung cancer treatment

Area of Science:

• Oncolytic virotherapy
• Microbial therapeutics
• Cancer immunotherapy

Background:

• Oncolytic viruses (OVs) show promise for cancer therapy but face challenges in lung cancer treatment, including biological barriers and immunosuppression.
• Effective delivery of OVs to lung tumors remains a significant hurdle for clinical application.

Purpose of the Study:

• To develop an inhalable microbe-OV consortium to overcome delivery barriers in lung cancer.
• To enhance the efficacy of oncolytic adenoviruses (Ads) through a synergistic microbial-viral approach.

Main Methods:

• Conjugation of PEGylated adenoviruses (Ads) to motile algae (Synechococcus WH8102) using click chemistry to form an inhalable consortium.
• Utilizing algal motility for mucus and epithelial barrier penetration and intratumoral calcium ion deprivation to disrupt tight junctions.
• Evaluating the consortium's efficacy in a murine lung tumor model via inhalation administration.

Main Results:

• The microbe-OV consortium successfully penetrated respiratory mucus and epithelial barriers.
• Algal-mediated calcium ion deprivation facilitated deep tumor penetration and enhanced Ads-induced immunogenic cell death (ICD).
• Inhalation administration of the consortium demonstrated significant antitumor effectiveness in a preclinical lung cancer model.

Conclusions:

• The inhalable microbe-OV consortium represents a novel strategy for overcoming biological barriers in lung cancer therapy.
• This synergistic approach potentiates OV-mediated ICD and enhances co-activated antitumor immunity.
• The developed strategy offers a promising platform for clinical translation of oncolytic microorganism biotherapeutics.