Health
Nanoimmunotherapy developed to improve lung cancer treatment
Researchers at Brigham and Women's Hospital, a founding member of the Massachusetts Integrated Brigham Health System, have developed a new nanomedicine therapy that delivers anti-cancer drugs to lung cancer cells and enhances the immune system's ability to fight cancer. The team showed promising results with the new therapy in laboratory cancer cells and in a mouse lung tumor model, which could potentially be applied to improve treatment and outcomes for patients whose tumors have not responded to traditional immunotherapy. The findings include: Scientific advances.
“Nanoparticles have been used for many years to deliver targeted drugs to tumor cells, but immunotherapy has also brought about a paradigm shift in how we treat cancer by preventing cancer cells from evading the immune system,” said Dr. Tanmoy Saha, a lecturer in medicine and researcher in the Department of Engineering at the Brigham School of Medicine and lead author of the paper. “Here, we've essentially combined these two approaches into one drug delivery system to treat non-small cell lung cancer.”
Lung cancer is the leading cause of cancer deaths worldwide, accounting for more than a quarter of cancer-related deaths. Non-small cell lung cancer (NSCLC) is the most common form, accounting for approximately 85% of all lung cancer cases. One common treatment for NSCLC is the use of immune checkpoint inhibitors, a class of drugs that block certain proteins that stop the immune system from killing cancer cells. However, most patients with NSCLC do not respond to these drugs. The main reason is that the treatments target only one protein, most commonly PD-L1, and that protein is not abundantly expressed in most lung cancer tumors. As a result, many patients must undergo a combination of chemotherapy and immunotherapy, which results in prolonged side effects and toxicity.
This new treatment works by delivering nanoparticles loaded with anti-cancer drugs directly to the tumor site, where antibodies attached to the nanoparticles bind to two different proteins (CD47 and PD-L1) on cancer cells. This dual approach allows both the innate and adaptive immune systems to find and destroy cancer cells, minimizing the toxicity commonly associated with existing cancer treatments.
“This system works with a kind of Velcro effect: instead of just looking for one protein on a cancer cell that an antibody can grab onto, these nanoparticles have two proteins,” said Shiladitya Sengupta, PhD, an associate professor of medical and biological engineering in the Brigham School of Medical Engineering and senior author on the paper. “So even if a cancer cell doesn't express one of the proteins that the nanoparticle targets, it can still attach to the other protein and deliver the drug loaded into the nanoparticle directly to the cancer tissue.”
The researchers set out to discover proteins expressed by lung tumors. They examined tissue from more than 80 lung cancer patients. Once the proteins were identified, they selected antibodies to target them. They then functionalized the antibodies with nanoparticles that already contained anticancer drugs.
Saha and his colleagues first tested the efficacy of the nanoparticles in the lab by visualizing how well the antibodies bound to cancer cells. They performed a series of experiments to evaluate and visualize the nanoparticles' binding strength and drug delivery capabilities. They then tested the efficacy of the conjugates in mouse models of two types of lung cancer. They found that the mice's cancer cells internalized the drug and that tumor size was reduced without any significant side effects or toxicity.
A limitation of this study is that so far, the treatment has only been tested on human tissue in the lab and in mouse models. More thorough toxicology studies need to be conducted before proceeding to clinical trials. In the future, the researchers hope to apply this technology to the treatment of other types of cancer by investigating additional antibodies and therapeutics that work with this nanomedicine approach.
“While we have seen some success with this drug delivery platform in preclinical trials, we must remember that the physiology of mice and humans is completely different. Further research is needed before we can bring this concept into clinical trials, but we are excited to see how this approach can transform cancer treatment,” Saha said.
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Sources 2/ https://www.sciencedaily.com/releases/2024/06/240614141933.htm The mention sources can contact us to remove/changing this article |
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