Houston Methodist scientists have developed a nanodevice to deliver immunotherapy to treat triple-negative breast cancer without side effects. Alessandro Grattoni, PhD, chair of the Department of Nanomedicine, and E. Brian Butler, MD, chair of the Department of Radiation Oncology, collaborated with a team from the University of Texas MD Anderson Cancer Center to establish a novel strategy to deliver immunotherapy directly into a tumor.

They are exploring whether the new path to nanodelivery could be more effective, with less side effects, compared to conventional immunotherapy, which is administered to the patient’s entire body. This new approach places the implantable nanodevice inside the tumor very accurately, using just one, simple procedure. Once implanted, the device is able to sustain delivery of the immunotherapy over a prolonged period of time without requiring the patient to return for numerous treatments.

“Timing of the release may be extremely important,” said Butler. “These immunotherapy payloads come in a tiny metal device with nanochannels that release the medication at a constant rate in a controlled way for extended periods of time.”

\This platform technology can be applied to many different types of cancer, but the team chose to work on triple-negative breast cancer for its dearth of treatment options. An added benefit beyond the sustained release system is that the implantable device can be placed inside the tumor with high accuracy, which also serves as a fiducial marker to facilitate precise delivery for image-guided radiation.

While the nanodelivery system has proven as effective as systemic delivery of immunotherapy, the next phase of preclinical trials will explore whether combining the device with radiation therapy can improve on the current effectiveness each achieves singly.

“Using Dr. Grattoni’s nanodevice in conjunction with our clinic, we hope to create a very robust immunological response, by putting the immunotherapy directly into the tumor, which is where all the information is,” Butler said. “This may harness the full power of a person’s immune system to destroy the cancer, offering the opportunity to get the systemic response, while treating locally, without all the side effects.”

“Our implant releases the drug in a constant manner until the entire amount is completely gone from the reservoir. Since it can deliver the immunotherapy by itself for weeks to potentially months, we would only need to place the device inside the tumor once and then the drug would be released autonomously for that long period of time.” – Alessandro Grattoni, PhD, Chair, Department of Nanomedicine, Professor of Nanomedicine, Houston Methodist.

The work was supported by grants from Golfers Against Cancer, the Nancy Owens Breast Cancer Foundation, and start-up funds from the Houston Methodist Research Institute. Chua CYX, Jain P, Susnjar A, Rhudy J, Folci M, Ballerini A, Gilbert A, Singh S, Bruno G, Filgueira CS, Yee C, Butler EB, Grattoni A. Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer. Journal of Controlled Release. 2018 Sept 10: 285: 23-34