Researchers at Houston Methodist have discovered a means to treat pancreatic cancer, one of the most aggressive and difficult-to-treat malignancies, by administering immunotherapy straight into the tumor with a device the size of a grain of rice.
In a paper recently published in Advanced Science, Houston Methodist Research Institute researchers used an implantable nanofluidic device they invented to deliver CD40 monoclonal antibodies (mAb), a promising immunotherapeutic agent, at a sustained low-dose via the nanofluidic drug-eluting seed (NDES).
In mice studies, the result was tumor shrinkage at a fourfold lower dosage than typical systemic immunotherapy treatment.
“One of the most exciting findings was that even though the NDES device was only inserted in one of two tumors in the same animal model, we noted shrinkage in the tumor without the device,” said Corrine Ying Xuan Chua, Ph.D., co-corresponding author and assistant professor of nanomedicine at Houston Methodist Academic Institute.
“This means that local treatment with immunotherapy was able to activate the immune response to target other tumors. In fact, one animal model remained tumor-free for the 100-days of continued observation.”
Pancreatic ductal adenocarcinoma is frequently diagnosed at advanced stages. In fact, about 85% of patients already have metastatic disease at diagnosis.
Our goal is to transform the way cancer is treated. 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.
Alessandro Grattoni
Immunotherapy has the potential to treat tumors that previously had no treatment options. However, because immunotherapy is administered throughout the body, it causes numerous side effects that can be long-lasting, if not life-long.
By directing the delivery directly into the tumor, the body is shielded from hazardous medications and suffers fewer side effects, allowing patients receiving therapy to enjoy a higher quality of life.
“Our goal is to transform the way cancer is treated. 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,” said Alessandro Grattoni, Ph.D., co-corresponding author and chair of the Department of Nanomedicine at Houston Methodist Research Institute.
On the International Space Station, Houston Methodist researchers are investigating similar nanofluidic delivery technology. At Houston Methodist, Grattoni’s nanomedicine lab works on implantable nanofluidics-based platforms for regulated and long-term medication administration and cell transplantation to treat chronic diseases.
The NDES device is made up of a stainless-steel drug reservoir with nanochannels that form a membrane that enables for sustained diffusion of the drug when it is released.
Other medical technology companies provide intratumoral drug-eluting implants for cancer therapeutics, but they are only intended for short-term use. The Houston Methodist nanofluidic device is designed for long-term controlled and sustained release, minimizing the need for recurrent systemic treatment, which can have negative side effects.
More lab research is being conducted to determine the efficacy and safety of this delivery technology, but researchers hope to see it become a viable option for cancer patients within the next five years.
Houston Methodist Research Institute collaborators on this study include Hsuan-Chen Liu, Daniel Davila Gonzalez, Dixita Ishani Viswanath, Robin Shae Vander Pol, Shani Zakiya Saunders, Nicola Di Trani, Yitian Xu, Junjun Zheng and Shu-Hsia Chen.
