Pam3CSK4-CDGSFAugments 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, Pam3CSK4-CDGSF. Conjugating CDGSFwith Pam3CSK4increased the stability and intracellular delivery. In addition, by synergistically activating the STING and TLR pathways, Pam3CSK4-CDGSFwas able to enhance immune activation. Both humoral and cellular immune responses were triggered by Pam3CSK4-CDGSFplus 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 Pam3CSK4-CDGSFcan serve as a potent adjuvant for vaccine construction to augment antitumor immunotherapy.