Breast Cancer Immunotherapy Delivered without Side Effects

While cancer immunotherapy is one of the most exciting new research areas due to the potential it holds for treating tumors that have been resistant to traditional therapies, it often still comes with unwanted side effects. Mitigating these negative reactions is a primary goal of clinicians and scientists. One possible mechanism to help diminish side-effects and off-target effects would be to deliver the drug directly to tumors and cancer cells – a strategy that has been notoriously difficult to accomplish.

However now, scientists at the Houston Methodist Research Institute have developed a nanodevice to deliver immunotherapy without side effects to treat triple-negative breast cancer. This new direct-to-tumor drug-delivery device makes it possible to deliver a one-time, sustained-release dose that would eliminate the need for patients to undergo several IV treatments over time. This tiny device is smaller than a grain of rice and, once inserted inside a tumor, can deliver the medication by gradually releasing the drug from its reservoir. Findings from the new study were published recently in the Journal of Controlled Release through an article titled “Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer.”

“With this research we are trying to establish a novel strategy to deliver immunotherapy straight into a tumor instead of delivering it to the whole body of a patient,” explains senior study investigator Alessandro Grattoni, Ph.D., chairman of the department of nanomedicine at the Houston Methodist Research Institute and inventor of the new device. “And we’re trying to understand whether delivering it this way would actually be more effective and have fewer side effects as compared to conventional immunotherapy, which today is given to the entire body of the patient.”

Dr. Grattoni and his team are not alone in studying ways to administer immunotherapeutics intratumorally. However, what distinguishes his approach from others is the use of the implantable nanodevice that can be placed inside the tumor very accurately, with just one, simple procedure and with the ability to sustain the delivery of the immunotherapy over a prolonged period.

“Timing of the release may be extremely important,” remarks co-senior study investigator E. Brian Butler, M.D., chair of the department of radiation oncology at Houston Methodist. “These immunotherapy payloads Dr. Grattoni created come in a little metal device with nanochannels that release the medication at a constant rate in a controlled way.”

The Houston Methodist team noted that by providing sustained doses, their implant maintains an active level of the drug for extended periods of time. This would reduce the need for continual clinic visits, which are usually required for immunotherapy and other cancer treatments.

Conversely, most other methods currently under preclinical and clinical trials require multiple injections into the tumor and, in many instances, necessitate repeated invasive procedures to access it. Moreover, injecting drugs straight into a tumor as a single dose may not be very effective, as only a part of it will stay, with the rest being rapidly eliminated due to the high-pressure nature of a tumor’s microenvironment. Dr. Grattoni’s intratumoral sustained-delivery method prevents this from happening.

“We’re in the middle of an exciting time in medicine because if we can get it to work, you decrease the toxicities to the patient,” Dr. Butler comments. “This offers the opportunity of treating locally and getting the systemic response without all the side effects.”

“Our implant releases the drug in a constant manner until the entire amount is completely gone from the reservoir,” Dr. Grattoni adds. “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.”

While this platform technology can be applied to many different types of cancer, they chose to work on triple-negative breast cancer, since there’s not currently a good therapeutic approach for treating patients that are affected by the disease. Breast cancer is traditionally not considered immunogenic, which means it may not respond well to immunotherapy, but triple-negative breast cancer (TNBC) is more immunogenic than other breast cancer subtypes. This is another reason why the researchers chose to focus on it. They are trying to make TNBC more responsive to the treatment with their implant.

“In this study, we demonstrated in mice that our intratumoral delivery of immunotherapy was equally effective compared to systemic immunotherapy treatment,” Dr. Grattoni says. “The difference was that the systemic immunotherapy showed significant side effects, while our device delivered the same effective treatment without side effects. We were, in fact, able to eliminate side effects, which was very surprising to us.”

The next phase of their research, also in mice, will be to combine the device with radiation therapy to see if this approach can improve on the effectiveness currently achieved through the systemic delivery of immunotherapy and not just equal it.

“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,” Dr. Butler concludes. “This will allow us to possibly 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.”