Abstract of the Year No. 1: Catheter-Directed Organ-Targeting Immune Augmentation Using a Nanoparticle-Based Therapeutic in a Rat de Novo HCC Model
Presentation: Wednesday, April 2, at 8 a.m.
A new study evaluating the use of intra-arterial administration of immune modulating nanoparticles to tumors in rats indicates promising results for anew area of interventional oncology.
The study sought to determine whether selective intra-arterial administration of PD-L1-conjugated nanoparticles (Antigen Release Agent and Checkpoint Inhibitor, ARAC) would have therapeutic benefits for hepatocellular carcinoma.
Kentaro Yamada, MD, PhD
Khashayar Farsad, MD, PhD, FSIR
“Liver cancer is still one of the leading causes of cancer deaths,” said Kentaro Yamada, MD, PhD, of Oregon Health & Science University. “Usually, we treat this cancer using transarterial chemoembolization or utilizing immune check inhibitors and molecular targeting agents. But the outcomes of these therapies are not fully satisfactory yet.”
There are two tumor types in terms of immunity, Dr. Yamada said: the cold tumor and hot tumor. Cold tumors, he said, are essentially invisible in terms of the anti-tumor immune system. HCC tumors are regarded as cold tumors. “That’s one of the reasons why the immune checkpoint inhibitors or molecular targeting agents don’t have a satisfactory outcome on tumor environment.”
Dr. Yamada said his team was inspired by the research of Wassana Yantasee, PhD, and Moataz Reda, PhD, on the use of novel nanoparticle-based therapeutics, which are traditionally delivered intravenously. Based on their data, Dr. Yamada and his team wanted to apply IR techniques to deliver the nanoparticles, such as transcatheter intra-arterial delivery. There is very little to no research in this area.
Researchers utilized a study concept created by Khashayar Farsad, MD, PhD, FSIR, which divided rats with MRI-confirmed HCC into two groups: one untreated, and one that received two courses of nanoparticle injections at a 7-day interval. The nanoparticle includes three agents: a PD-L1 antibody that is already used in clinical practice to reactivate anti-tumor T cells, a PLK1inhibitor that directly inhibits tumor cell division and a CPG molecule that stimulates anti-tumor immunity.
By combining these three agents into one nanoparticle and delivering it intra-arterially, physicians are able to not only enhance antitumor immunity directly in the cell but also convert a cold tumor—which is invisible to systemic anti-tumor immunity—into a hot tumor that can become sensitive to anti-tumor immunity therapies.
Results
Researchers found that not only did the nanoparticle induce sufficient immune response but they were also able to bypass artery embolization.
“Usually for liver cancer treatment, we need to embolize the feeding tumor, which can cause side effects,” Dr. Yamada said. “With nanoparticles, you do not need to embolize the artery into the tumor, and as a result the therapeutic agent is retained within the tumor.”
In addition, researchers were able to dramatically cut the dosage delivered to just 10% of the dose required for systemic IV injection determined by their previous study—thereby reducing both systemic side effects and costs.
Because researchers were seeking to determine whether this therapy was even compatible with intra-arterial delivery, they did not follow additional endpoints such as survival benefit—though they have plans to evaluate that in the future. In addition, researchers are working on applying this approach to additional cancer models, such as pancreatic cancer, lung cancer and hepatic metastasis from colorectal cancer.
“We are hopeful that IR techniques can be used not just to treat tumors we can see with our own eyes or with CT imaging, but also to address the tumor immune environment at the microscopic level,” Dr. Yamada said.
“Currently, there are a few FDA approved nanoparticle-based therapeutics that can release a chemotherapy agent, but they are not utilized in IR practice. Additionally, there are no nanoparticle-based therapeutics that act on the tumor immune environment,” Dr. Yamada said.
“Our result is still in the preliminary stage, but hopefully our early results can facilitate this kind of nanoparticle based platform study in interventional oncology,” he said.
