Houston Methodist nanomedicine researchers have found a way to tame pancreatic cancer – one of the most aggressive and difficult to treat – by delivering immunotherapy directly to the tumor with a device smaller than a grain of rice.
In a paper recently published in Advanced Science, Houston Methodist Research Institute researchers used an implantable nanofluid device they invented to deliver CD40 monoclonal antibody (mAb), a promising immunotherapeutic agent, at low, sustained doses via seed eluting of a nanofluid drug. (NDES). The result, found in a murine model, was tumor reduction at a dose four times lower than traditional systemic immunotherapy treatment.
“One of the most exciting findings was that even though the NDES device was only inserted into one of the two tumors in the same animal model, we recorded tumor shrinkage without the device.” says Corrine Ying Xuan Chua, Ph.D., correspondent author and assistant professor of nanomedicine at the Houston Methodist Academic Institute. “This means that local treatment with immunotherapy is able to activate the immune response to target other tumors. In fact, one animal model remained tumor-free through 100 days of follow-up.”
Pancreatic ductal adenocarcinoma is often diagnosed at an advanced stage. In fact, about 85% of patients already have metastatic disease at the time of diagnosis.
The Houston Methodist researchers are studying a similar nanofluid delivery technology on board the International Space Station. The Grattoni nanomedicine lab at Houston Methodist is focused on implantable nanofluid-based platforms for controlled and long-term drug delivery and cell transplantation to treat chronic diseases.
Immunotherapy has shown promise in treating cancers that previously lacked good treatment options. However, because immunotherapy is administered throughout the body, it causes many side effects that sometimes last a long time, if not lifelong. By focusing delivery directly to the tumor, the body is protected from exposure to toxic drugs and fewer side effects, which essentially allows patients undergoing treatment to have a better quality of life.
“Our goal is to change the way cancer is treated. We see this device as a viable approach to penetrate pancreatic tumors in a minimally invasive and effective way, enabling more focused therapy using less drugs,says Alessandro Grattoni, Ph.D., correspondent author and chair of the Department of Nanomedicine at the Houston Methodist Research Institute.
The NDES device consists of a stainless steel drug reservoir containing nanochannels, thereby creating a membrane that allows continuous diffusion as the drug is released.
Other medical technology companies offer intratumoral drug-eluting implants for cancer therapy, but are intended for shorter duration use. The Houston Methodist nanofluid device is intended for long-term sustained, controlled release, avoiding repeated systemic treatments that often cause adverse side effects.
Additional laboratory studies are underway to determine the effectiveness and safety of this delivery technology, but researchers want to see it become a viable option for cancer patients in the next five years.
The Houston Methodist Research Institute collaborators on this study included 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.
This research received financial support from Golfers Against Cancer and the National Institutes of Health (NIH-NIGMS R01GM127558).