Florida State University researchers are giving oncologists another tool in their fight against pediatric brain cancer.

In work published in Bioactive Materials, a research team led by Department of Chemistry and Biochemistry Professor Qing-Xiang “Amy” Sang showed the possibility of enhancing natural killer immune cells to improve their ability to attack a rare pediatric brain cancer.

”Natural killer cells are the policemen of the body,” Sang said. “They patrol the body and recognize viruses, bacteria and other pathogens, as well as cancer cells. Our goal is to enhance both the quantity and quality of these cells, making them more potent in their ability to combat cancer.”

Natural killer cells can target all types of cancer, and previous research has examined their effectiveness as a therapy. But this is the first study to test the ability of natural killer cells to destroy a specific variety of cancer known as a malignant rhabdoid tumor. When this tumor appears in the central nervous system, it is called an atypical teratoid rhabdoid tumor (ATRT). Although it is a rare disease, it accounts for 20% of all central nervous system tumors in children younger than 3.

“It’s a major unmet clinical need,” Sang said. “We still don’t have a standard, optimized therapy for children with cancer, especially children with brain cancer.”

Natural killer cells are a critical part of the human immune system, but they can be overwhelmed by cancer cells. Sang’s research team wanted to see if they could help the fight against this disease and develop a treatment with fewer side effects than traditional approaches such as chemotherapy or radiation therapy.

The researchers derived natural killer cells from human-induced pluripotent stem cells — cells from skin or blood that have been reprogrammed back into an embryonic-like state, allowing them to develop into any type of human cell. Unlike feeder cells from mice, which are typically used in similar studies, human-induced pluripotent stem cell-derived natural killer cells don’t pose a risk of rejection by a patient’s immune system.

They also enhanced the immune quality of those cells by using different proteins to stimulate them to have a stronger killing power.

Although more work is needed to develop a ready-to-use therapy for cancer patients, the research shows that natural killer cells derived from human-induced pluripotent stem cells could be the basis for future medicines to treat pediatric brain tumors.

“These findings pave the way for developing a safer and more effective immunotherapy for children with brain cancer,” Sang said.

This research built upon Sang’s previous work that was supported by several  initiatives at FSU, including a grant from the FSU Council on Research and Creativity, the Pfeiffer Professorship for Cancer Research in Chemistry and Biochemistry from the College of Arts and Sciences, and an Endowed Chair Professorship in Cancer Research.

“FSU has been great in supporting cancer research and also rare pediatric disease research,” she said. “We used that seed funding to do preliminary studies to test novel ideas and get the project started. FSU has been very good in funding innovative ideas and new projects that enabled us to compete for external funding.”

This work was mainly supported by grants from the Florida Department of Health’s Live Like Bella Pediatric Cancer Research Initiative. It was also partially supported by the National Science Foundation and the FSU Institute for Pediatric Rare Diseases.

Co-authors on this work were graduate researchers Sonia Kiran, Yu Xue and Drishty Badhon Sarker in the Department of Chemistry and Biochemistry in the College of Arts and Sciences, and Yan Li, a professor in the Department of Chemical and Biomedical Engineering in the FAMU-FSU College of Engineering.

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When doctors are examining suspected cancer cases, they turn to biomarker tests to help make a diagnosis.

With a testing system and patient samples, physicians can investigate potential leads, narrowing down their list of culprits to provide precise, effective treatment for patients.

A team led by Florida State University chemists has developed a new test for detecting biological markers related to several types of cancer. Their research was recently published in Journal of the American Chemical Society.

“Better tools for detecting cancer mean more effective treatment for patients,” said study co-author Hedi Mattoussi, a professor in the FSU Department of Chemistry and Biochemistry. “Our goal in this research was to build a biosensor that would light up in the presence of cancer markers, offering another tool for the ongoing problem of detecting this disease.”

The sensing platform is made of a gold nanoparticle and molecules called peptides that are labeled with a dye. The components are connected by chemical bonds, and the gold nanoparticle keeps the dye from glowing in the presence of UV light. When a patient sample containing the enzyme MMP-14 — a biomarker for various types of cancers, but most commonly for breast cancer — is added, it breaks bonds in the peptides, separating a fragment with the dye from the gold. Without the gold to absorb the energy from the dye, the sample begins to glow.

“You start with a system that is dark, which we can think of as ‘off,’ like we would with a light switch,” Mattoussi said. “When you bring in the enzyme, the system turns ‘on’ and emits light. It is like a beacon.”

The light glowing from the sample depends on the concentration of the enzyme and interaction time. By measuring that light, researchers can generate data that inform them if a cancer marker is present in a sample and in what levels.

Various tests already exist for examining whether a patient has cancer. This research is a first step toward developing a method that can test for a wider variety of cancers.

Mattoussi and his team tested their system with the MMP-14 enzyme but they plan to expand this research with work that matches more peptide chains with other enzyme cancer markers. With further development, it could allow scientists to use a single assessment to test for a variety of cancers at once.

“The platform we have designed is applicable to any enzyme,” he said. “All that you need to do is vary the nature of the peptide that is attached to the nanoparticle. You change the peptide, you change the enzyme, and it works the same way.

Along with its applications for detecting disease, the research also sheds more light on how enzymes interact with peptides that are attached to nanoparticles and how the addition of enzymes affects the testing system.

“One aspect of our research was the application aspect,” Mattoussi said. “Cancer diagnosis is still a huge problem. Early detection has been a limiting factor. But the other aspect of this work was the ability to develop a platform that starts with a nanoparticle attached to a peptide labeled with a dye and understand the way they interact. How efficient are those interactions? What happens when you vary the size of nanoparticles or the number of peptides? So, there is a practical aspect and a fundamental aspect to this research.”

Co-authors on this paper were Zhicheng Jin, a former FSU doctoral student who is now a postdoctoral associate at Harvard University, Narjes Dridi, Goutam Palui, who is now a researcher at the U.S. Food and Drug Administration, and Professor Qing-Xiang “Amy” Sang, all from FSU; Valle Palomo and Philip E. Dawson, of The Scripps Research Institute; and Jesse V. Jokerst of University of California San Diego.

This work was funded by the National Science Foundation, the Air Force Office of Scientific Research and Kasei-Asahi Corporation.

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