Pancreatic Cancer Device Uses Revolutionary Nanofluidic Approach to Transform Tumor Microenvironment

Feb. 9, 2024 - Eden McCleskey

Houston Methodist researchers have developed an ultra-tiny device that administers immunotherapy drugs directly into pancreatic cancer tumors, a promising approach to bypass the disease's notoriously impenetrable system of self-defense.

In a recent mouse study, the research team showed that delivery by nanofluidic drug-eluting seeds (NDES) modulated the immune microenvironment of the tumor and reduced the burden of the most common type of pancreatic cancer.

"Our goal with this research is to transform the way cancer is treated," said Alessandro Grattoni, Ph.D., chair of the Department of Nanomedicine at Houston Methodist and the study's primary investigator. "We see this device as a viable approach to penetrating the pancreatic tumor in a minimally invasive and effective manner, allowing for a more focused therapy using less medication."

The approach requires just a quarter dose of the drug, CD40 agonist monoclonal antibodies, required for systemic treatment, according to the study, recently published in Advanced Science. The technique is similar to brachytherapy seed insertion for prostate cancer.

Pancreatic ductal adenocarcinoma (PDAC), which accounts for about 90% of cases of pancreatic cancer, is widely regarded as one of the most challenging tumors to treat because it is so good at evading the immune system. Although many adult cancers have seen remarkable turnarounds in recent decades thanks to new drugs and immunotherapies, pancreatic cancer's five-year survival rate has remained a stubbornly low 8%.

The researchers are hopeful that the miniscule implants — smaller than a grain of rice — will finally be able to get around PDAC's notoriously strong defenses.

"Conventional and even novel therapies are ineffective against pancreatic cancer unless the disease happens to be detected extremely early," said Grattoni. "An immune system evading tumor microenvironment and very dense tumor stroma blockading medication delivery are crucial factors in fostering pancreatic cancer's growth and metastasis."

Seeking an effective work-around, Grattoni, Corrine Ying Xuan Chua, Ph.D., and a team of investigators designed the NDES platform to administer sustained low-dose CD40 mAb directly into the tumor itself.

Although the research team believes they are several years away from a clinical trial in humans, the groundbreaking study confirms NDES proof of concept and paves the way for future therapies using a more targeted, less invasive approach.

Click here to read an in-depth Methodology article highlighting the innovative research.

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