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Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial

A personalized vaccine to treat glioblastoma, a fast-growing and incurable brain cancer that affects four in 100,000 people in the U.S., is safe and elicits robust and broad immune responses that appears to increase recurrence-free survival in a subset of patients after surgery, according to an early-stage clinical trial co-led by researchers at Washington University School of Medicine in St. Louis.

In patients with an especially aggressive form of glioblastoma, the vaccine caused no serious side effects and prolonged patients’ overall survival compared to historical outcomes after standard-of-care surgery and chemo-radiotherapy. One long-term survivor remains recurrence-free nearly five years later.

The results of the phase 1 trial, conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, were published May 12 in Nature Cancer. The study was led jointly by Mass General Brigham and Geneos Therapeutics, a Philadelphia-based biotechnology company.

“We are extremely encouraged by these results,” said Tanner M. Johanns, MD, PhD, lead author of the study and an assistant professor in the Division of Oncology in the John T. Milliken Department of Medicine at WashU Medicine. “This kind of vaccine is a first for glioblastoma, and it is exciting to think how we can leverage this individualized therapeutic DNA cancer vaccine platform to make a positive impact on the lives of patients who are fighting this disease. Additionally, combination therapies leveraging this personalized platform are currently being investigated at WashU to test if outcomes may be improved further.”

Abstract: Nature Cancer

Johanns and colleagues report the results (including safety, efficacy and immunogenicity) of a phase 1 clinical trial of a DNA-based personalized therapeutic cancer vaccine administered following surgical resection and radiation in patients with MGMT unmethylated glioblastoma.

Continue reading “Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial” | >

3D-printed ceramic implants that mimic human bone could enable patient-matched repair

Researchers at Tampere University, Finland, have developed a groundbreaking 3D-printed ceramic implant material that closely mimics real human bone. The findings advance the development of personalized bone regeneration and may lead to more effective and accessible treatments for bone defects.

The research article, titled “Biomimetic bone calcium phosphate-based scaffolds fabricated via ceramic vat photopolymerization: Effect of porosity, sintering temperature, mineralogical phases and trace elements on the osteogenic potential,” was published in Materials Today Bio.

Bone grafting is the second most common tissue transplantation procedure worldwide, with more than 2 million operations performed annually. Current treatments often rely on bone taken from the patient or a donor, approaches that are limited in availability and may involve additional surgery, lengthy recovery times and complications. As populations age, the need for safer and more effective alternatives is growing rapidly.

Targeting PI3Kδ suppresses pancreatic cancer by dual disruption of fibrosis and immune evasion

In this study, we identify an unexpected and previously unrecognized role for PI3Kδ in promoting stromal fibrosis in PDAC, expanding its known function beyond immune regulation. Through mechanistic and preclinical studies, we show that PI3Kδ controls the biosynthesis of LPA in cancer cells and stromal fibroblasts, establishing an immunometabolic axis that sustains both fibrosis and immune evasion in PDAC.

Strikingly, PI3Kδ inhibition alone was sufficient to suppress tumor growth, reduce fibrosis, restore antitumor immune responses, and prolong survival across multiple PDAC models. Dual inhibition of PI3Kδ and ATX produced additive effects on stromal remodeling and immune activation, significantly enhancing responsiveness to chemotherapy and PD-1 blockade. These findings position PI3Kδ as a central regulator of the PDAC tumor microenvironment and highlight its therapeutic targeting, alone or in combination, as a promising strategy to treat PDAC.

Cell therapy offers ‘real hope’ for people living with cirrhosis

A pioneering treatment which could slow or reverse liver failure and offer a potential alternative to liver transplants has shown positive results in a medical trial.

70% of end-stage liver disease patients who were treated with macrophage cell therapy in the MATCH trial did not need a liver transplant after four years, compared with just 40% who didn’t receive the treatment.

The cell therapy takes immune cells from the patients’ blood and turns them into mature macrophages – a white blood cell – which is then re-injected back into the patient. The macrophages travel to the liver, where they break down scar tissue, reduce inflammation, and encourage the growth of healthy liver cells.

Hippocampal ripples and replay reveal how brain recombines past knowledge for flexible planning

When facing new situations or problems, humans typically rely on knowledge they acquired in the past. Specifically, neuroscience studies suggest that the brain reorganizes past experiences and previously acquired knowledge, creating mental frameworks that can help humans to solve the problems they are facing. The recombination of past knowledge into new mental structures also allows humans to flexibly plan future actions in changing environments. Past studies suggest that two key brain regions contribute to this process, the hippocampus and the medial prefrontal cortex (mPFC).

The hippocampus is a brain structure that plays a key role in the formation of memories and spatial navigation. The mPFC, on the other hand, is known to support decision-making, planning, reasoning and the integration of information.

Researchers at Beijing Normal University, the Chinese Academy of Medical Sciences, University College London (UCL) and other institutes recently set out to investigate how the hippocampus and mPFC work together to combine past knowledge into new configurations. Their findings, published in Nature Neuroscience, suggest that this process is supported by brief bursts of high-frequency neural activity in the hippocampus, called hippocampal ripples, and the replay (i.e., re-activation) of past experiences in the brain.

Physicists create hybrid light-matter particles that interact strongly enough to compute

Eighty years ago, Penn researchers J. Presper Eckert and John Mauchly launched the age of electronic computing by harnessing electrons to solve complex numerical problems with ENIAC, the world’s first general-purpose electronic computer. Today, that same architecture still underlies general computing, but electrons are beginning to show their limits. Because they carry a charge, they lose energy as heat, encounter resistance as they move through materials, and become harder to manage as chips incorporate more transistors and handle larger volumes of data.

With artificial intelligence pushing today’s hardware to process, move, and cool more, Penn physicists led by Bo Zhen in the School of Arts & Sciences are looking to the electron’s massless counterpart, the photon, to shoulder more of the load.

“Because they are charge-neutral and have zero rest mass, photons can carry information quickly over long distances with minimal loss, dominating communications technology,” explains Li He, co-first author of a paper published in Physical Review Letters and a former postdoctoral researcher in the Zhen Lab. “But that neutrality means they barely interact with their environment, making them bad at the sort of signal-switching logic that computers depend on.”

Sustainable chemistry: Iron substitutes noble metals in catalytic reactions

The production of many products used in everyday life and in industry, such as pharmaceuticals, plastics, and coatings, requires chemical catalysts, often expensive noble metals with limited availability. Researchers at the Karlsruhe Institute of Technology (KIT) are now presenting the first air-stable iron compound, which enables the direct use of iron(I) for catalysis and, unlike previous methods, does not require strong reducing agents. A first test yielded active iron catalysts.

The study, “A Simple, Air Stable Single-Ion Source of Iron(I),” is published in the Journal of the American Chemical Society.

Catalysts are required to speed up chemical reactions or even make them possible at all. The catalysts generally used in industry are noble metals, such as rhodium, iridium, or palladium. They are highly effective for many applications, but at the same time expensive and rare.

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