5'-Phosphorothioester Linked Cyclic Dinucleotides, Endo-S-CDNs, Displaying Impressive Antitumor Activities In Vivo...

Area of Science:

• Immunology
• Pharmacology
• Oncology

Background:

• Cyclic dinucleotides (CDNs) activate the cGAS-STING pathway, popular in cancer immunotherapy.
• Existing CDN analogs require intratumor administration, limiting clinical application for difficult-to-reach tumors.

Purpose of the Study:

• Evaluate the in vivo efficacy of novel endo-S-CDNs as STING agonists.
• Conduct structure-activity relationship studies for optimized endo-S-CDN development.
• Assess the potential for subcutaneous administration of endo-S-CDNs.

Main Methods:

• Structure-activity relationship analysis of endo-S-CDN analogs.
• In vivo efficacy studies in MC38 and B16-F10 tumor models.
• Subcutaneous administration of endo-S-CDNs.

Main Results:

• Identified potent endo-S-CDNs with STING agonist activity.
• Demonstrated robust anti-tumor protection in vivo via subcutaneous injection.
• Confirmed efficacy against both MC38 and B16-F10 tumor models.

Conclusions:

• Endo-S-CDNs are effective STING agonists suitable for subcutaneous delivery.
• Subcutaneous administration of endo-S-CDNs provides significant anti-tumor efficacy.
• These findings support the clinical potential of endo-S-CDNs as a convenient cancer immunotherapy.