Reproductive safety of STING agonists MSA-2 and manganese-MSA-2

MSA-2, as an oral molecule for activating STING signaling pathway to cure the tumor entering clinical trials. The toxicity of MSA-2 has aroused wide concern, especially the reproductive toxicity can not be ignored. We synthesized the STING agonist (MSA-2) and its derivative manganese-MSA-2 (MSA-2-Mn) and investigated the reproductive toxicity. We evaluated the reproductive effects of MSA-2 and MSA-2-Mn in female mice under the administration alone and on the reproductive system of male mice in the presence or absence of combined radiation. Results suggested that MSA-2 and MSA-2-Mn have negligible reproductive toxicity in healthy adults. Conclusions: This provides new ideas to enhance the efficacy of immunotherapy, as well as favorable evidence for future systemic dosing in patients of reproductive age and clinical trials of immunotherapy.