Pam3CSK4-CDGSF Augments Antitumor Immunotherapy by Synergistically Activating TLR1/2 and STING

Abstract

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-CDG^SF. Conjugating CDG^SF with Pam₃CSK₄ increased the stability and intracellular delivery. In addition, by synergistically activating the STING and TLR pathways, Pam₃CSK₄-CDG^SF was able to enhance immune activation. Both humoral and cellular immune responses were triggered by Pam₃CSK₄-CDG^SF 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 Pam₃CSK₄-CDG^SF can serve as a potent adjuvant for vaccine construction to augment antitumor immunotherapy.