CAR-T therapy has revolutionized treatments for many hematologic malignancies, but it has shown far less efficacy against solid tumors. One reason for this lower efficacy in solid tumors is increased antigen heterogeneity. This study utilizes a ligand-based CAR-T approach, which allows targeting of multiple receptors by a single ligand. A high expression of the ligand oncostatin M’s (OSM) receptors, oncostatin M receptor (OSMR), and/or leukemic inhibitory factor receptor (LIFR) were noted in osteosarcoma cell lines and patient samples. Osteosarcoma is a bone cancer where treatment options have been stagnant for close to 40 years. Thus, this study explores the therapeutic potential of OSM ligand-based CAR-T cells against osteosarcoma.
Third-generation CAR-T cells expressing human OSM on their surface were created, with the surface expression of OSM confirmed by flow cytometry. Co-incubation of OSM CARs and osteosarcoma in vitro was performed, with cell death assessed via Incucyte and PI detection by flow cytometry. CAR-Ts were injected i.v. into mice with osteosarcoma cell line xenografts, and metastatic osteosarcoma. New patient-derived samples were tested for OSMR and LIFR expression and vulnerability to OSM CAR T cells. A new PDX model (named KKOS) from a patient with metastatic treatment-resistant osteosarcoma was characterized and tested for its susceptibility to OSM CAR T cells. All cytotoxic in vivo experiments were performed with n =3–6 mice per group per experiment.
OSM-CAR-T cells displayed cytotoxicity against osteosarcoma cell lines and patient samples expressing either one of OSM’s receptors in vitro and in vivo. Large increases in cytokine release, specifically IFNγ, were noted in a target-specific manner. One injection of OSM-CAR-T cells intravenously reduced tumor burden in two different mouse xenograft models. A similar anti-tumor effect was also noted in a metastatic model and a mouse model with multiple implanted KKOS tumors.
Researchers at McGill University have developed a novel device that generates sound-like particles known as phonons at extremely cold temperatures. The technology could be used to create phonon lasers, with possible applications in communications and medical diagnostics.
“Modern communication is largely based on light, including electromagnetic waves and electrical currents. In a medium such as oceans, sound can travel, whereas light and electrical currents cannot,” said Michael Hilke. “In the human body, sound waves can also be a useful tool.”
Hilke is Associate Professor of Physics and co-author of the study published in Physical Review Letters. The device was built and analyzed at McGill and the National Research Council of Canada. The material was synthesized at Princeton University.
Researchers in the University of Minnesota Twin Cities have discovered a powerful new way to control the electronic behavior of a metal—by manipulating the atomic properties of materials where they meet. The study, published in Nature Communications, demonstrates that interfacial polarization can tune the surface work function of metallic ruthenium dioxide (RuO2) by more than 1 electron volt (eV)—a tiny amount of energy—simply by adjusting film thickness at the nanometer scale.
“We often think of polarization as something that belongs to insulators or ferroelectrics—not metals,” said Bharat Jalan, professor and Shell Chair in the Department of Chemical Engineering and Materials Science at the University of Minnesota. “Our work shows that, through careful interface design, you can stabilize polarization in a metallic system and use it as a knob to tune electronic properties. This opens an entirely new way of thinking about controlling metals.”
This specific change is most powerful when the metal layer is about 4 nanometers thick—roughly the width of a single strand of DNA. At this precise size, the metal shifts from being “stretched” by the material underneath it to a more “relaxed” state. This transition proves that the physical way atoms are packed together has a direct, measurable impact on how the metal handles electricity.
Discovered in 2019, the material known as nickelates has intrigued researchers for its potential to become a superconductor at elevated temperatures—a property that could significantly advance such fields as quantum science and energy transmission. However, it’s a very unstable material and difficult to work with. But the lab of Professor Charles Ahn has developed a method that could enhance superconductivity in these materials. The results are published in Nature Communications.
With their ability to conduct electricity with no resistance, superconductors are a key component to quantum computing, medical imaging, and a number of other fields. A group of copper-oxide compounds known as cuprates have long been central to the study of high-temperature superconductivity (“high temperature” is a relative term—they still need to be kept in very cold environments). Nickelates are especially exciting because they share some of cuprates’ key electronic features while offering a new platform for materials design and tuning.
Enter nickelates, a material with many similarities to cuprates, but with the potential to eventually become even more useful to scientists. Dung Vu, a postdoctoral associate who led the study, noted that synthesizing nickelate thin films is “notoriously difficult.” The Ahn lab is one of the few in the world with the ability to do so.
MIT researchers discovered a paradoxical phenomenon in optical physics that could enable a new bioimaging method that’s faster and higher-resolution than existing technology. They discovered that, under the right conditions, a chaotic mess of laser light can spontaneously self-organize into a highly focused “pencil beam.”
Using this self-organized pencil beam, the researchers captured 3D images of the human blood-brain barrier 25 times faster than the gold-standard method, while maintaining comparable resolution. By showing individual cells absorbing drugs in real-time, this technology could help scientists test whether new drugs for neurodegenerative diseases like Alzheimer’s or ALS reach their targets in the brain, with greater speed and resolution.
“The common belief in the field is that if you crank up the power in this type of laser, the light will inevitably become chaotic. But we proved that this is not the case. We followed the evidence, embraced the uncertainty, and found a way to let the light organize itself into a novel solution for bioimaging,” says Sixian You, assistant professor in the MIT Department of Electrical Engineering and Computer Science (EECS), a member of the Research Laboratory for Electronics, and senior author of a paper on this imaging technique.
Scientists are making a major leap toward freezing organs for future use without damaging them. A new study reveals that one of the biggest obstacles—cracking during ultra-cold preservation—can be reduced by carefully tuning the temperature at which tissues enter a glass-like state. This breakthrough builds on recent successes in cryopreserved organ transplants and could bring the long-imagined idea of “banking” organs for later use much closer to reality.