Advances in Cancer Treatment

The NDES Device

"One of the most exciting findings was that even though the NDES [nanofluidic drug-eluting seed] device was only inserted in one of two tumours in the same animal model, we noted shrinkage in the tumour without the device."

"This means that local treatment with immunotherapy was able to activate the immune response to target other tumours."

"In fact, one animal model remained tumour-free for the 100 days of continuous observation."

Corrine Ying Xuan Chua, assistant professor of nanomedicine, Houston Methodist Academic Institute

"Our goal is to transform the way cancer is treated."

"We see this device as a viable approach to penetrating the pancreatic tumour in a minimally invasive and effective manner, allowing for a more focused therapy using less medication."

Alessandro Gratoni, chair, department of nanomedicine, Houston Methodist Research Institute

Pancreatic cancer is one of the most aggressive forms of cancer. A small organ situated behind the stomach, the pancreas produces enzymes and hormones assisting the body in breaking down food to convert it to energy. Pancreatic cancer symptoms usually appear only once tumours have begun to take their toll on the body, which makes its presence difficult to detect. Patient prognosis varies dependent on how early in its development the cancer is detected. In Canada, the five-year net survival rate for pancreatic cancer stands at ten percent.

The most common treatment used in cancers that are difficult to treat and which have few treatment options available. is immunotherapy. Owing to the fact that immunotherapy is delivered throughout the entire body, the risk of side-effects that can last a lifetime, come with the therapy. Patients can expect fewer side-effects and a better quality of life during treatment, if the treatment area can be narrowed to the tumour site specifically, sparing the rest of the body from toxic chemical exposure.

A new and hugely promising technique has been advanced, detailed in the journal Advanced Sciences. The technique makes use of an implantable device smaller in size than a grain of rice. This device has been designed to deliver immunotherapy directly into pancreatic tumours. Called an NDES device, it can deliver sustained doses of CD40 monoclonal antibodies (mAb), and was shown to reduce tumours in mice models even though a fourfold lower dosage than what is required for traditional immunotherapy was used.

The nanofluidic drug-eluting seed (NDES) device includes a stainless-steel reservoir which contains nanochannels allowing for the sustained diffusion of CD40 monoclonal antibodies, an immunotherapeutic agent of great promise. Patients can avoid repeated infusions -- and corresponding side-effects that can accompany traditional immunotherapy -- because the device has been designed to be used over the long term.

More research is required, but the team from the department of nanomedicine at Houston Methodist Research Institute anticipates that the device will become a viable option for treatment of cancer patients within the following five years.

Houston Methodist Research Institute nanomedicine researchers used an implantable nanofluidic device smaller than a grain of rice to deliver immunotherapy directly into a pancreatic tumor. Credit: Houston Methodist

Study Abstract

"Agonist CD40 monoclonal antibodies (mAb) is a promising immunotherapeutic agent for cold-to-hot tumor immune microenvironment (TIME) conversion. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer known as an immune desert, and therefore urgently needs more effective treatment. Conventional systemic treatment fails to effectively penetrate the characteristic dense tumor stroma. Here, it is shown that sustained low-dose intratumoral delivery of CD40 mAb via the nanofluidic drug-eluting seed (NDES) can modulate the TIME to reduce tumor burden in murine models. NDES achieves tumor reduction at a fourfold lower dosage than systemic treatment while avoiding treatment-related adverse events. Further, abscopal responses are shown where intratumoral treatment yields growth inhibition in distant untreated tumors. Overall, the NDES is presented as a viable approach to penetrate the PDAC immune barrier in a minimally invasive and effective manner, for the overarching goal of transforming treatment."