cGAMP (Cyclic AMP-GMP) is a cyclic dinucleotide that acts as a second messenger in mammalian cells and is synthesized "on demand" when cells are threatened[1, 2]. cGAMP activates the stimulator of interferon genes (STING), triggering a signaling cascade that leads to the production of type I interferons and other immune mediators[3]. Under cGAMP stimulation, cells show increased IFNB1 transcription, but no abnormal transcription of genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF)[4].
In vitro, treatment of mouse bone marrow-derived dendritic cells and human peripheral blood mononuclear cell-derived dendritic cells with cGAMP (5mg/mL, 60mg/mL) for 24h directly activated both mouse and human dendritic cells. The purity of CD11c+ cells in the tested cell populations was 95% for human peripheral blood mononuclear cell-derived dendritic cells and 82% for mouse bone marrow-derived dendritic cells[5].
In vivo, cGAMP (5μg) administered as a nasal mucosal adjuvant to immunized mice promoted antigen-specific proliferation of mouse splenocytes and enhanced antigen-specific humoral immune responses[5].
References:
[1] Liu Y, Fei Y, Wang X, et al. Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity[J]. Molecular Therapy, 2023, 31(7): 1938-1959.
[2] Su Y. Development of Riboswitch-based Sensors for High-throughput Enzyme Activity Screens[M]. University of California, Berkeley, 2018.
[3] Kaushal A. A central role of stimulator of interferon genes’ adaptor protein in defensive immune response[J]. Immunologic Research, 2025, 73(1): 39.
[4] Liu Y, Jesus A A, Marrero B, et al. Activated STING in a vascular and pulmonary syndrome[J]. New England Journal of Medicine, 2014, 371(6): 507-518.
[5] Škrnjug I, Guzmán C A, Ruecker C. Cyclic GMP-AMP displays mucosal adjuvant activity in mice[J]. PloS one, 2014, 9(10): e110150.
cGAMP (Cyclic AMP-GMP)是一种环状二核苷酸，是哺乳动物细胞内的第二信使，是在细胞受到威胁时“即时”合成的[1, 2]。cGAMP (Cyclic AMP-GMP)激活干扰素基因刺激因子（STING），激活导致产生I型干扰素和其他免疫介质的信号级联[3]。在cGAMP (Cyclic AMP-GMP)刺激下，细胞显示IFNB1转录增加，但编码白介素-1（IL1）、白介素-6（IL6）或肿瘤坏死因子（TNF）基因的转录无异常[4]。
在体外，cGAMP (Cyclic AMP-GMP)（5mg/mL, 60mg/mL）处理小鼠骨髓来源树突状细胞和人外周血单核细胞来源树突状细胞24h，直接激活了小鼠和人树突状细胞。测试细胞群体中CD11c+细胞的纯度，人外周血单核细胞来源的树突状细胞为95%，小鼠骨髓来源的树突状细胞为82%[5]。
在体内，cGAMP (Cyclic AMP-GMP)（5μg）通过鼻黏膜佐剂处理免疫小鼠，促进了小鼠脾细胞的抗原特异性增殖能力，促进了抗原特异性体液免疫反应[5]。