This website uses a security service to protect against malicious bots. This page is displayed while the website verifies you are not a bot.
Get the latest international news and world events from around the world.
Tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance
Fc-gamma receptors (FcγRs) regulate IgG antibody activity, and Fc-engineering is a proven method to improve the efficacy of tumor-targeting antibodies. Here, we explore tailored FcγR blockade to enhance the therapeutic efficacy and tolerability of immune checkpoint-blocking (ICB) antibodies.
Mechanistically matched murine surrogate and human lead FcγR-blocking and immune checkpoint-blocking antibodies were used to study whether tailored FcγR-blockade, targeting FcγRIIB selectively or all FcγRs, can enhance the efficacy and overcome resistance to immune checkpoint therapy in vivo and in vitro. Mechanistic studies were performed with clinical reagents, including ipilimumab, nivolumab, pembrolizumab, and human FcγRIIB-selective (BI-1607) and pan-FcγR-blocking (BI-1206) antibodies, using human cells and transgenic animals with clinically relevant expression of immune checkpoint receptors.
We demonstrate that FcγRIIB-selective and pan-FcγR-blocking antibodies increase the in vivo efficacy of αCTLA-4 and αPD-1 antibodies, respectively. FcγRIIB-selective antibody enhancement of αCTLA-4 was associated with increased intratumoral Treg depletion, myeloid reprogramming, interferon-γ and CXCL10-induction, and increased activated effector CD8+ T cells, correlating with higher activating-to-inhibitory (A: I) FcγR engagement ratios. Conversely, pan-FcγR blockade protected αPD-1-coated T cells from macrophage phagocytosis, increasing intratumoral activated CD8+ T cells by decreasing activating and inhibitory FcγRs.
Smart sensor identifies present molecules by remembering the past
Most sensors are designed to do only one thing: detect what passes through them. But what if a sensor could do more? To create a new generation of technology, researchers have looked to living systems for inspiration. If a sensor could detect molecules, could it also remember previous interactions and selectively respond to them?
Researchers have developed a device that does exactly that on a tiny scale, laying the groundwork for a new generation of smart molecular sensors.
In an article recently published in ACS Nano, researchers from SANKEN at the University of Osaka and collaborating institutions created an autonomous solid-state nanopore that can sense molecules, generate electrical signals and retain memories of recent events without external control. Unlike conventional nanopores, which act as passive channels, the new device continuously changes its own structure through chemical reactions, creating a dynamic sensing environment that responds to molecules passing through it.
Hypereosinophilia With Pseudomonas aeruginosa Infection in Patients With Asthma on AntiInterleukin5 Biologics
Biologic therapies targeting IL-5 or its receptor reduce eosinophilia and exacerbations in asthma. Breakthrough eosinophilic attacks are usually considered biologic failure. We report 2 patients with severe asthma receiving mepolizumab or benralizumab who developed relapsing hypereosinophilia associated with Pseudomonas aeruginosa airway infection. Case 1 was a 71-year-old woman in Canada with severe eosinophilic asthma and COPD overlap whose eosinophils suddenly rebounded to 1,400 cells/μL during an acute exacerbation while on mepolizumab, coinciding with P aeruginosa infection and resolving after antibiotic treatment.
Johns Hopkins’ AI-powered, voice-controlled robot performs autonomous surgery
Researchers at Johns Hopkins University have shown that an artificial intelligence-powered robot—trained on videos of previous surgeries—could learn how to perform the procedure itself, without help from a human operator.
According to the university, the autonomous system was able to adapt to the natural variations in anatomy between simulated patients, and react correctly to unplanned events in real-time—such as the introduction of blood-like dyes that obscured the surrounding tissue. It was also able to recover on its own from initially missed instrument placements.
Aging restricts maturation of CXCL13+ T follicular helper cells in human immunity
Bracey et al. show that impaired antibody responses with age are primarily driven by defective T follicular helper cell maturation rather than intrinsic B cell dysfunction. They identify loss of human-specific CXCL13 + T follicular helper cells and reduced BACH2 and SOX4 as hallmarks of aging-associated humoral immune dysfunction.
Eye contact helps infants ‘tune in’ to speaker’s brainwaves and learn language
Infants use eye contact with speakers to work out what to pay attention to and synchronize their brainwaves, helping them learn language, scientists in Cambridge and Singapore have shown.
Infants are surrounded by a vast range of stimuli that compete for their attention—sights, sounds and voices—and must somehow work out which things are worth paying attention to and learning from. To do this, they often rely on social cues—eye contact, “baby talk” or someone calling their name, for example—but how this helps with learning is not clear.
Victoria Leong and colleagues at the University of Cambridge, UK, and Nanyang Technological University (NTU), Singapore, have previously shown that when an infant and adult make eye contact, their brainwaves synchronize with each other.