DENVER & CHICAGO– TriSalus Life Sciences, an emerging immuno-oncology company committed to transforming outcomes for patients with liver and pancreatic tumors, today announced data presented at the American Association of Cancer Research showing that regional delivery of oligodeoxynucleotide 2395 (ODN2395) activated the toll-like receptor 9 (TLR9), resulting in reduced tumor burden of liver metastases in mice.1
ODNs bind and activate TLR9 to initiate an immune response against certain cancer cells.2 TLR9 agonists (TLR9A) activate both the innate and adaptive immune systems, and play an important role in antiviral and anti-tumor immunity.3 TLR agonists have been administered via different routes based on the therapeutic purpose, however, delivery of TLR agonists into liver tumors by direct needle injection has been clinically challenging, particularly in the setting of a large tumor burden.
The pre-clinical study presented at AACR, conducted by Chandra C. Ghosh and fellow researchers at Roger Williams Medical Center, examined the impact of metastatic liver disease in 12 mice, which were randomized to receive either 1, 3, 10 or 30 micrograms of the TLR9A, ODN2395, through the portal vein (PV) or 30 micrograms administered intravenously (IV). The study showed regional delivery of the TLR9A through the PV at the 30 micrograms dose level was superior to systemic IV administration with respect to control of liver metastases and reduction of liver myeloid-derived suppressor cells (MDSC), which play a crucial role in solid tumor immunosuppression, in addition to favorable effects on liver macrophage subsets.
“Understanding the impact of delivery route on the ability of TLR9 agonists to control liver metastases and favorably modulate the immune microenvironment may help unleash the potential to use the immune system to fight cancer,” said Steven Katz, M.D., Chief Medical Officer, TriSalus Life Sciences. “This foundational work will help us tap into the potential of integrating novel therapeutics with drug delivery technology to better penetrate solid tumors.”
Solid tumors continue to represent one of the single biggest hurdles to successful cancer treatment.4 High levels of pressure inside solid tumors prevent the delivery of oncology therapeutics, with less than 1% of therapy penetrating solid tumors in some circumstances.5,6 TriSalus developed PEDD to deliver immuno-oncology therapeutics directly into the vasculature of solid tumors with the potential for minimizing systemic toxicity.
