Researchers at Brigham and Women’s Hospital have created a new nanomedicine treatment that transports anticancer medications to lung cancer cells and boosts the immune system’s ability to combat cancer. The team demonstrated the promising potential of this therapy in lab-grown cancer cells and in mouse models with lung tumors. This new treatment could benefit patients with tumors that have not responded to traditional immunotherapy. The Brigham and Women’s Hospital is a founding member of the Mass General Brigham healthcare system.The team successfully demonstrated the potential of a new therapy in cancer cells and mouse lung tumor models. This therapy could potentially improve outcomes for patients with tumors that have not responded to traditional immunotherapy. Their research has been published in the journal Science Advances.
“Nanoparticles have a history of delivering targeted medication to tumor cells, and immunotherapy has changed the way we approach cancer treatment by preventing cancer cells from evading the immune system,” said the team leader.Tanmoy Saha, PhD, an instructor of medicine and researcher in the Division of Engineering in Medicine at the Brigham, stated, ”Here, we’ve essentially combined these two approaches into one drug delivery system to address non-small cell lung cancer.”
Lung cancer is the primary cause of cancer-related deaths worldwide, responsible for over a quarter of all cancer deaths. Non-small cell lung cancer (NSCLC) is the most prevalent form, accounting for approximately 85 percent of all lung cancer cases. One of the commonly used treatments for NSCLC is the utilization of immune checkpoint inhibitors, a category of drugs that obstruct certain proteins that hinder the immune system.new therapy delivers a cancer-fighting drug directly to the tumor site using nanoparticles. The nanoparticles are equipped with antibodies that target two proteins (CD47 and PD-L1) on cancer cells. This dual approach aims to address the limited effectiveness of current treatments, which often only target one protein, such as PD-L1, that is not abundantly expressed in most lung cancer tumors. As a result, many NSCLC patients do not respond to these drugs and must undergo a combination of chemo and immunotherapies, leading to enduring side effects and toxicities.Adaptive immune systems are being used to target and eliminate cancer cells with the goal of reducing the side effects commonly associated with current cancer treatments.
Senior author Shiladitya Sengupta, PhD, an associate professor of medicine and bioengineer in the Division of Engineering in Medicine at the Brigham, explained that the system operates with a Velcro-like effect. Instead of targeting just one protein on a cancer cell, the nanoparticles have two. This means that if a cancer cell does not express one of the proteins targeted by the nanoparticle, it can still attach to the other one and deliver the drug loaded into the nanoparticle.The study focused on delivering anticancer drugs directly to lung tumors. The researchers analyzed the proteins expressed by lung tumors in over 80 patients’ tissue. They then selected antibodies to target these proteins and attached them to nanoparticles loaded with the anticancer drug. The effectiveness of the nanoparticle was tested by observing its binding to cancerous cells in the lab and conducting experiments to assess its drug delivery capabilities.Afterward, they evaluated the effectiveness of the compound in mice that had two different types of lung cancer. They discovered that the cancer cells in the mice absorbed the medication, resulting in a reduction in tumor size with no significant negative effects or harmful reactions.
It’s important to note that, at this point, the treatment has only been tested on human tissue in a laboratory setting and in mice. Before moving on to clinical trials, it needs to undergo more extensive testing for potential toxic effects. In the future, the researchers aim to modify this technology to treat various other types of cancer by investigating different antibodies and treatments that could be compatible with this nanomedicine.
According to Saha, although the drug delivery platform has shown promise in preclinical testing, it is crucial to recognize the differences between mouse and human physiology. Further studies are needed before the concept can advance to clinical trials. Nonetheless, there is enthusiasm about the potential for this approach to revolutionize cancer care.
