Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China.
Chem Commun (Camb). 2021 Jan 14;57(4):504-507. doi: 10.1039/d0cc06959k. Epub 2020 Dec 17.
A novel STING agonist, CDG, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDG might be a site for covalent conjugation. Injection of CDG generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV-2 spike protein using CDG as an adjuvant elicited an exceptionally high antibody titer and a robust T cell response, overcoming the drawbacks of aluminum hydroxide. These results highlighted the therapeutic potential of CDG for cancer immunotherapy and the adjuvant potential of the STING agonist in the SARS-CoV-2 vaccine for the first time.
一种新型 STING 激动剂 CDG 被合成，其在同侧被修饰为硫代磷酸酯和氟。CDG 中的硫代磷酸酯可能是共价连接的位点。注射 CDG 可产生免疫原性（“热”）的肿瘤微环境，从而更有效地抑制黑色素瘤，比二硫代 CDG 更有效。特别是，使用 CDG 作为佐剂接种 SARS-CoV-2 刺突蛋白可引发异常高的抗体滴度和强大的 T 细胞反应，克服了氢氧化铝的缺点。这些结果首次强调了 CDG 在癌症免疫治疗中的治疗潜力，以及 STING 激动剂在 SARS-CoV-2 疫苗中的佐剂潜力。
