News & Events
TriSalus Life Sciences’ Pressure-Enabled Drug Delivery™ (PEDD™) Increases Penetration and Antitumor Activity of Anti-CEA CAR-T in Mouse Model of Liver Metastases
High-pressure PEDD delivery of chimeric antigen receptor T cell (CAR-T) significantly increased antitumor activity compared with low-pressure delivery
No increase in liver inflammation or toxicity
PEDD -18% tumor burden compared to +148 in low-pressure delivery (P=0.05), and +178% in saline controls º(P=0.04)
Check point inhibitors delivered regionally with high-pressure PEDD also significantly increased the therapeutic index for colorectal liver metastases, while limiting systemic exposure
May 11, 2019—A preclinical trial to be presented at the annual meeting of the American Association of Immunologists (AAI) demonstrates that administering anti–carcinoembryonic antigen (anti-CEA) CAR-T to liver metastases using high delivery pressure in an animal model simulating TriSalus™ Life Sciences’ innovative Pressure-Enabled Drug Delivery™ (PEDD™) significantly increased penetration and antitumor activity when compared with standard low-pressure (LP) delivery.
PEDD delivery of CAR-T: Increased penetration, greater therapeutic effect
In the anti-CEA CAR-T study performed by Dr. Steven Katz, MD, director of the Office of Therapeutic Development at the Roger Williams Medical Center, mice with CEA+ liver metastases were infused employing simulated PEDD technology (HP cohort) or by standard means (LP cohort). Hepatic interstitial fluid pressures were simultaneously recorded. One day after infusion, flow cytometry assessment demonstrated a significantly greater cell therapy product delivery in the PEDD/HP cohort, 15.9% CD3+CAR, compared with 5.1% in the LP cohort (P=0.0004).
“Higher delivery pressure, such as that achieved with TriSalus devices in patients, correlated with higher CAR-T penetration that better controlled tumor growth,” said Dr. Katz, who is also the principal investigator of the ongoing clinical Phase 1b trial using Sorrento’s (Sorrento Therapeutics, Inc. [NASDAQ: SRNE]) CEA–CAR-T cells for the treatment of liver metastases. “We have seen excellent CEA–CAR-T delivery in our clinical studies using PEDD. Follow-up to this proof-of-concept study will investigate combination approaches, with the goal of durable tumor eradication.”
PEDD delivery of checkpoint inhibitors shown to reduce colorectal liver metastases — even with 10- fold lower dose
In a separate poster presentation at the AAI annual meeting, significant increases in therapeutic index also occurred when PEDD was used to deliver anti–PD-1 checkpoint inhibitors (CPI) regionally to colorectal liver metastases.
In this study, mice with colorectal liver metastases treated with regional PEDD high-pressure delivery (HP cohort) were administered a 3- or 10-fold lower dose of CPI than is typically given systemically to patients. Mice treated with regional HP CPI infusions showed significantly lower tumor burden than animals given a low-pressure (LP) infusion (P=0.04 and P=0.0001, respectively) at early time points. Importantly, HP regional delivery at the lower doses resulted in similar tumor control to mice receiving conventional systemic doses, with significantly less systemic CPI exposure.
“These results add to the growing body of clinical evidence that TriSalus Life Sciences’ PEDD technology overpowers high pressure to penetrate solid tumors and enhance the reach and efficacy of therapeutic agents while reducing systemic toxicity,” said Mary T. Szela, CEO and president of TriSalus Life Sciences.
About TriSalusLife Sciences
TriSalus Life Sciences is dedicated to improving patient outcomes in pancreatic and other highly intractable solid tumors. TriSalus™ Infusion Systems have the potential to deliver diagnostic, therapeutic agents, and immuno-stimulants directly into tumor vasculature powered by its proprietary Pressure-Enabled Drug Delivery™ (PEDD™) approach with SmartValve™ technology to improve the distribution and penetration of therapy in solid tumors. This innovative approach has the potential to allow for the administration of multiple mechanisms that can work together to overcome inherent immune suppression within the solid tumor microenvironment.