Effects of oncolytic bacteria, SGN1, against a broad spectrum of malignancies in preclinical and clinical studies

e15184 Background: It has been widely reported over the past 40 years that almost all human cancer cells examined are strongly dependent on methionine for growth and metastasis, largely owing to the deficiency of cancer cells in methionine salvage pathway. To specifically deprive cancer tissues of methionine without affecting systemic methionine content, we have developed the first oncolytic bacteria drug, SGN1, that is based on the attenuated Salmonella typhimurium and its tumor targeting ability, and overexpresses an L-methioninase gene. Currently, SGN1 has been approved for, and entered, clinical trials in the US and Taiwan, China (NCT05103345 & NCT05038150). Methods: Cellular and animal models were used for examining the tumor-targeting effects and safety profiles of SGN1. We calculated the role of engineered Salmonella in cancer cells by RNA-seq analysis. Results: In preclinical cellular and xenograft models, SGN1 specifically targeted solid tumors， induced a sharp regression of several very divergent models of human carcinomas, caused a significant decrease of tumor cell invasion, and essentially eliminated the growth and metastasis of the xenograft tumors. RNA-Seq analysis revealed that the engineered Salmonella reduced the expression of a series of genes promoting cell growth, cell migration and invasion. Like the original attenuated Salmonella typhimurium (VNP20009), SGN1 has displayed excellent safety profiles based on the GLP-evaluation in multiple animal models. In preclinical human tumor-derived models, SGN1 exhibited strong inhibitory effects on tumor growth and metastasis in a broad spectrum of tumors, including, but not limited to, small cell lung carcinoma, osteosarcoma, hepatocellular cancer, breast cancer (including triple negative breast cancer), pancreatic cancer, prostate cancer, and cervical cancer. In investigator-initiated trial (IIT) studies, SGN1 significantly shrank, or completely lysed, patients’ tumor and ameliorated cachexia, while patients showed no severe adverse reaction except some transient fever and nausea. Conclusions: The first-in-class oncolytic bacteria, SGN1, featured with the ability of tumor-targeting and methionine hydrolysis, exhibits broad-spectrum antitumor activity and great potential for cancer therapy. Clinical trial information: NCT05038150 . Clinical trial information: NCT05103345 .