SIL204, a treatment being developed by Israeli company Silexion Therapeutics Corp., may help the immune system identify and attack KRAS-driven cancers, according to preclinical findings released on Wednesday.
Combined with the company's previous data, the findings support SIL204's potential to combat three different ways cancerous tumors evade the immune system: by making the cancer cells more visible to the system, restoring susceptibility to cell death from the system, and reducing a checkpoint molecule that allows the cells to evade the system's surveillance.
The treatment uses small RNA molecules, known as siRNA, to suppress the expression of mutated KRAS genes, one of the main mechanisms behind tumor growth within certain cancer patients. KRAS mutations occur in roughly 90% of pancreatic cancers and 30 - 35% of lung adenocarcinomas.
In studies on human cancer cell lines representing three different KRAS mutations in human pancreatic and non-small cell lung cancer, SIL204 treatment led to statistically significant increases in expression of FAS, an immune "death receptor" which allows the immune system to trigger programmed cell death. It also led to a significant reduction in expression of HLA-G, an immune checkpoint.
"These new findings meaningfully extend and reinforce the immuno-oncology profile of SIL204 that we first
reported in May. We believe this profile supports the rationale for further evaluation of SIL204 in combination with
anti-PD-(L)1 checkpoint inhibitor therapies, particularly in indications like pancreatic cancer where these agents
have historically shown limited single-agent efficacy," Chairman and CEO of Silexion Ilan Hadar said.
SIL204 enters new phase as trial starts
This comes as the oncology research field explores combining KRAS-directed treatments with checkpoint inhibitors.
Silexion advanced SIL204 into Phase 2/3 clinical evaluation at the end of July, after beginning its first clinical trial at Tel Aviv Sourasky Medical Center. The trial is focused on patients with pancreatic cancer and, while initially limited to this one hospital, is later expected to expand to additional medical centers in Israel, Germany, and other countries.
Follow us on Google
