PamCSK-CDG Augments Antitumor Immunotherapy by Synergistically Activating TLR1/2 and STING.

Cyclic dinucleotides (CDNs), agonists of stimulator of interferon genes (STING), are promising agents for immunotherapy. However, the application of CDNs has been limited by their instability and low transmembrane efficiency. Here, we introduced a conjugated adjuvant of STING and TLR1/2, PamCSK-CDG. Conjugating CDG with PamCSK increased the stability and intracellular delivery. In addition, by synergistically activating the STING and TLR pathways, PamCSK-CDG was able to enhance immune activation. Both humoral and cellular immune responses were triggered by PamCSK-CDG plus OVA (V4), and tumor growth was significantly inhibited after V4 administration. More importantly, V4 can also boost the antigen-specific CD8+ T cell response for cancer cell killing. Thus, the conjugated STING and TLR1/2 agonist PamCSK-CDG can serve as a potent adjuvant for vaccine construction to augment antitumor immunotherapy.