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.

中文翻译：

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Pam ₃ CSK ₄ -CDG ^SF通过协同激活TLR1 / 2和STING增强抗肿瘤免疫治疗

环二核苷酸（CDN）是干扰素基因（STING）刺激剂的激动剂，是用于免疫治疗的有希望的药物。但是，CDN的应用受到其不稳定和跨膜效率低的限制。在这里，我们介绍了STING和TLR1 / 2，Pam ₃ CSK ₄ -CDG ^SF的共轭佐剂。CDG ^SF与Pam ₃ CSK ₄共轭可增加稳定性和细胞内递送。另外，通过协同激活STING和TLR途径，Pam ₃ CSK ₄ -CDG ^SF能够增强免疫激活。Pam ₃ CSK触发体液和细胞免疫反应_4- CDG ^SF加OVA（V4），且在V4给药后肿瘤生长受到明显抑制。更重要的是，V4还可以增强抗原特异性CD8 + T细胞应答，从而杀死癌细胞。因此，缀合的STING和TLR1 / 2激动剂Pam ₃ CSK ₄ -CDG ^SF可以用作构建疫苗的有效佐剂，以增强抗肿瘤免疫治疗。