ODN2395 / TriSalus Life Sci - LARVOL DELTA

Pressure enabled drug delivery (PEDD) of nelitolimod increased therapeutic delivery, reduced immunosuppression, and improved efficacy in porcine and murine liver tumor models. (PubMed, Front Oncol) - "Transgenic pigs (oncopigs) with liver tumors received intra-arterial infusions of fluorescently labeled ODN2395 or nelitolimod either via PEDD with a specialized infusion device or with conventional microcatheter delivery in both lobar and selective infusions. PEDD of nelitolimod significantly reduced immunosuppressive MDSCs and an increase in cytotoxic CD8 + T cells within the LM. In conclusion, use of PEDD enhanced targeted therapeutic delivery in swine liver tumors and reduced tumor progression by promoting anti-tumor immunity in murine LM in association with suppressive myeloid cell elimination."

Journal • Preclinical • Cutaneous Melanoma • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Solid Tumor • CD8 • PTPRC

Regional infusion of a class C TLR9 agonist enhances liver tumor microenvironment reprogramming and MDSC reduction to improve responsiveness to systemic checkpoint inhibition. (PubMed, Cancer Gene Ther) - "Further, PBMC-derived human MDSCs express TLR9, and treatment with class C TLR9 agonists (ODN2395 and SD101) reduced the expansion of MDSC population. Regional TLR9 agonist infusion along with systemic anti-PD-1 therapy improved control of LM. With effective delivery, TLR9 agonists have the potential to favorably reprogram the liver TME through reduction of MDSCs and favorable macrophage polarization, which may improve responsiveness to systemic CPI therapy."

Biomarker • Checkpoint inhibition • Journal • Myeloid-derived suppressor cells • Tumor microenvironment • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • IL6

Improved Delivery of a TLR-9 Agonist to Liver Tissue by Intravascular Pressure Enabled Drug Delivery (PEDD) Compared with Direct Needle Injection (SIR 2022) - "The first cohort (n=4) received a hepatic arterial (HA) PEDD infusion of the TLR-9 agonist oligonucleotide ODN 2395 conjugated to an IRD800 nearIR fluorophore (ODN2395F), using a TriNav device (TNV-21120-35, TriSalus Life Sciences). The results of this study illustrate the advantage of the PEDD method for HA infusion of therapeutics such as SD-101 directly into hepatic tissue. A 7-fold increase in treated tissue volume and a 2.5-fold increase in therapeutic delivery using PEDD in the normal porcine liver relative to direct needle injection suggest that PEDD offers a potentially effective means of treating diffuse intrahepatic disease through targeted delivery."

Cutaneous Melanoma • Hepatology • Melanoma • Oncology • Solid Tumor

Regional delivery of a TLR9 agonist to boost checkpoint inhibitor responsiveness in liver metastases (SITC 2021) - "To study the impact of TLR9 activation on human MDSC, we treated healthy donor PBMCs with ODN-2395 or SD101. Increased PDL-1 expression in response to TLR9 stimulation among MDSC may further enhance the anti-PD-1 effect. Therefore, combing regional infusions of a TLR9 agonist with systemic anti-PD-1 agents may be a promising approach for liver tumor treatment."

Checkpoint inhibition • IO biomarker • Gastrointestinal Cancer • Liver Cancer • Oncology • Solid Tumor • CD33 • CSF2 • IFNA1 • IL10 • IL6 • ITGAM • PD-L1

[VIRTUAL] Regional administration of class C CpG Oligodeoxynucleotides results in superior intrahepatic TLR9 activation and immunomodulation compared to systemic infusion (AACR 2021) - "In this study, we evaluated the effect of class C ODN-2395 as TLR9A in inhibiting LM progression and its impact on the liver MDSC population...Western Blot data of tumor lysates show that ODN delivery by PV increased NFκB (pP65) activity and production of IL-6, significantly relative to IV. Overall, our data suggest that the regional delivery of a TLR9A has the potential to provide superior modulation of the TME within the liver.Table:"

Oncology • IL6 • ITGAM • PTPRC • TLR9

TriSalus Life Sciences Presents Data at American Association of Cancer Research Showing Reduced Liver Tumor Burden from Toll-Like Receptor Agonists (Businesswire) - "TriSalus Life Sciences...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....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."

Preclinical • Oncology