Researchers at NYU Langone Health developed a new drug that targets mutant HER2 cancer proteins without harming healthy cells.
The researchers say the new technique may lead to new ways to treat patients with some cancers with minimal side effects.For some proteins, a single mutation or change in their DNA instructions is all it takes to tip the balance between functioning normally and causing cancer.
But despite causing major diseases, these slightly mutated proteins can resemble their normal versions so closely that treatments designed to target mutants could also harm healthy cells. Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, a new study describes the development of a biologic, a drug derived from natural biological systems, that targets a mutant cancer protein called HER2 without attacking its nearly identical normal counterpart on healthy cells. While still in the early stages, the researchers say this technique could lead to new therapies to treat cancer patients with HER2 mutations with minimal side effects. “We set out to make an antibody that can recognize a single change in the 600 amino acid building blocks that make up the exposed part of the HER2 protein, which conventional wisdom says is very difficult,” said lead study author“The fact that we were able to detect the difference of a single amino acid so cleanly was a surprise.” The new findings revolve around HER2, a protein that occurs on the surfaces of many cell types and turns on signaling pathways that control cell growth. It can cause cancer when a single amino acid swap locks the protein into “always-active” mode, which in turn causes cells to divide and multiply uncontrollably. Cancer can also result when cells accidentally make extra copies of the DNA instructions that code for the normal version of HER2 and express higher protein levels on their surfaces.There are a few FDA-approved therapies, including trastuzumab and pertuzumab, that can treat this kind of cancer, but these therapies all work at the level of HER2 on the cell surface, where only low levels of the mutated version of HER2 occur. In addition, since some approved therapies cannot tell the difference between mutant and normal HER2, they are more likely to harm healthy cells expressing normal HER2., the study shows how the researchers harnessed their new protein-engineering technique to develop antibodies that recognize only mutant HER2. In a process miming natural antibody development, the researchers subjected antibodies to multiple rounds of mutation and selection, looking for variants that recognized mutant HER2 but not the normal version. By taking atomic images with a cryo-electron microscope, the team saw how their new antibodies interacted with HER2 spatially , allowing the team to refine their antibody designs continually. However, selectively recognizing mutant HER2 was only part of developing an effective cancer treatment since antibodies must work with the immune system to kill cancer cells. To address this challenge, the researchers converted their antibody into a bispecific T cell engager, a molecule in which the antibody targeting the mutant protein is fused to another antibody that binds to and activates T cells, an immune cell. One end of the antibody sticks to the mutant HER2 on a cancer cell, while the other triggers T cells to kill the cancer cell. Further testing showed this method killed mutant HER2 cancer cells in dishes but spared normal ones. The treatment significantly reduced tumor growth when the researchers tested their T cell engagers in mice with mutant HER2 tumors. It did so without causing weight loss or visible sickness in the mice, which suggested the treatment had few side effects in the animals. However, Dr. Koide noted that because there are differences between mouse and human proteins, it is possible the lack of obvious side effects stemmed from the antibody binding even less to mouse wild-type HER2 than to the human version. Future studies will tell.Kapil Kajal is an award-winning journalist with a diverse portfolio spanning defense, politics, technology, crime, environment, human rights, and foreign policy. His work has been featured in publications such as Janes, National Geographic, Al Jazeera, Rest of World, Mongabay, and Nikkei. Kapil holds a dual bachelor's degree in Electrical, Electronics, and Communication Engineering and a master’s diploma in journalism from the Institute of Journalism and New Media in Bangalore.
Cancel Treatment Cancer Cancer Cell Health
United States Latest News, United States Headlines
Similar News:You can also read news stories similar to this one that we have collected from other news sources.
Faculty of Life and Health Sciences: Advancing Human Health Through Rigorous ScienceThe Faculty of Life and Health Sciences is dedicated to advancing our understanding of human health by developing interdisciplinary fields and integrating international expertise. Led by world-class academicians, the faculty focuses on solving cutting-edge scientific problems and cultivating top innovative talents.
Read more »
$92 million North Hollywood Health Center to replace old public health buildingIt will include exam rooms, phlebotomy stations, a wellness center, a lab, community gardens and demonstration kitchen.
Read more »
Poor health of new Southern Resident orca calf concerns WA researchersA new Southern Resident orca calf was last seen looking unwell. Researchers mull over the implications of L128's fate.
Read more »
Researchers help redefine core microbiome, opening new chapter in precision healthResearchers have introduced a novel method for identifying the crucial set of gut microbes commonly found in humans and essential for health.
Read more »
Major Samsung Health update brings Health Records and expands the Medication tracking featureIzzy, a tech enthusiast and a key part of the PhoneArena team, specializes in delivering the latest mobile tech news and finding the best tech deals. Her interests extend to cybersecurity, phone design innovations, and camera capabilities.
Read more »
Researchers in a lab near Lake Erie study how toxic algae can damage healthIn a lab not far from the shores of Lake Erie, researchers are trying to learn more about the ways toxic algae can damage health. Steven Haller, a clinical researcher in the University of Toledo's department of medicine, says his interest dates back to a scare when toxic algae made it into his community's water supply a decade ago.
Read more »