Tag: Academic research

Researchers at Penn State University have developed a method to create 3D-printed soft electrodes that can conform to an individual brain surface to provide more accurate patient-specific tracking of biophysical signals in the brain. The study, published in Advanced Materials, details a new technique to create neural interfaces that improve upon current stiff methods to more closely conform to the complex structure of the brain.

“Each person has a different brain structure, depending on their height, weight, age, sex and more,” said Tao Zhou, PhD, Wormley Family Early Career Professor and corresponding author of the study. “Despite this, we try to fit neural interfaces onto brains like they have identical structures. This motivated us to create electrodes that are tailored for each individual, based on the structure of their brain.”

The new electrodes are created using hydrogel, a water-rich material that has properties similar to brain tissue, and built in a honeycomb-like internal structure to help balance flexibility and strength. These soft electrodes, dubbed HiPGE for honeycomb-inspired printable gel electrodes, are fabricated using a 3-D printing method called direct ink writing, which allows for precise shaping at very small scales. The honeycomb design reduces stiffness allowing the electrodes to stretch and conform to the brain’s ridges and grooves without damaging brain tissue.

To individualize the design process, a patient would first have an MRI scan, which is used to create detailed simulations of each brain scanned. The simulations inform the how to create the shape of each electrode so it aligns with the patient’s specific cortical folds. The team then 3D prints both the electrode and a model of the brain to test how closely the device fits. In experiments involving 21 human brain models, the printed electrodes demonstrated improved conformity compared to traditional designs.

“The unique gyral patterns of the human brain demand patient-specific neural interfaces to achieve precise neuromodulation, mitigate adverse tissue responses, and optimize therapeutic efficacy and safety,” the researchers wrote, noting that conventional rigid electrodes “exhibit limited conformability to the brain’s heterogeneous cortical topography,” resulting in “poor electrode-tissue contact, signal loss, and foreign body responses.”

To evaluate HiPGE performance and biological compatibility, the researchers conducted 28-day in vivo tests in rat models. Results from the tests showed that electrodes maintained stable function for the entire the testing period and did not trigger an immune response. The flexible electrodes also provided consistent and accurate readings of electrical and physiological signals in the brain.

Prior research has studied soft-material neural interfaces, but customization to individual gyral patterns has been limited. The introduction of a combined imaging, modeling and printing design workflow has solved this limitation by enabling electrodes to be tailored at the patient level.

The researchers wrote that the folded structure of the brain “creates a unique ‘fingerprint’ for each brain.” They also noted that current rigid devices can lead to “signal degradation due to scar formation,” and can create instability caused by the mismatch between the stiff neural interface materials and soft brain tissue.

Clinically, the improved contact between electrode and brain tissue could provide more reliable monitoring of neural activity, an important improvement for diagnosing and managing neurological conditions. Better signal fidelity could enhance applications such as brain-computer interfaces, neuroprosthetics, and neuromodulation therapies. The soft, conformable design may also reduce complications associated with long-term implantation, including inflammation and tissue damage.

“This tailored design ensures robust electrode-tissue integration, minimizing mechanical mismatch and improving signal fidelity during in vivo neural activity recording,” the researchers wrote. They added that studies “confirmed HiPGE’s biocompatibility, revealing no significant immune response or structural disruption to brain tissue.”

Future research will seek refine the technology for specific disease monitoring and exploring its use in clinical settings. They also aim to optimize the devices for targeted neurological conditions, which could inform the development of more precise and individualized care strategies.

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Chimeric antigen receptor (CAR) T cell therapies have transformed the treatment of certain blood cancers, yet translating this success to solid tumors has remained a major challenge. One of the key obstacles has been T cell exhaustion, a state in which engineered immune cells lose their ability to sustain an effective anti-tumor response.

Now, early clinical data from a first-in-human Phase I trial suggest a new approach may help overcome this limitation. Presenting at the AACR annual meeting in San Diego, researchers from the Perelman School of Medicine at the University of Pennsylvania report that a novel “KIR-CAR” T cell therapy shows promising safety and early efficacy signals across multiple solid tumor types.

New design inspired by natural killer cells

The investigational therapy, SynKIR-110, represents a departure from traditional CAR T designs. Rather than using a single-chain receptor, the therapy is modeled after natural killer (NK) cell receptors and uses a “multi-chain” architecture.

This design separates tumor recognition from activation, effectively creating an intrinsic “on-off” mechanism. The T cell remains in a resting state until it encounters its target, at which point the receptor components assemble to trigger an immune attack.

“The KIR-CAR design provides a natural ‘on-off’ mechanism, which helps avoid the problem of T cell exhaustion,” said Janos L. Tanyi, MD, PhD, principal investigator of the study. “The CAR turns on when it finds its target, kills it, and then rests, rather than constantly burning energy.”

This contrasts with conventional CAR T cells, which remain continuously active and can become depleted over time, limiting their effectiveness—particularly in the more complex microenvironment of solid tumors.

Early clinical signals in difficult-to-treat cancers

The Phase I dose-escalation trial enrolled nine patients with advanced, mesothelin-expressing cancers, including ovarian cancer, mesothelioma, and cholangiocarcinoma. These patients had limited treatment options, having received an average of four prior lines of therapy.

Although the primary goal of the study was to assess safety, early signs of efficacy were observed. Disease stabilization was reported in four patients, and one patient in the highest dose cohort achieved an ongoing partial response.

“These are cancer types that have never had an approved cell therapy,” Tanyi said. “We’re seeing good efficacy signals, even at low doses, and limited toxicity.”

The results suggest that the therapy may be able to generate meaningful anti-tumor responses even in heavily pretreated populations.

Favorable safety profile

Safety has been another major barrier for CAR T therapies, particularly in solid tumors. However, the KIR-CAR approach appears to mitigate some of these concerns.

No dose-limiting toxicities were observed in the initial cohorts. Cytokine release syndrome (CRS), a common side effect of CAR T therapy, occurred in 33% of patients but was limited to low-grade events. Notably, there were no cases of immune effector cell-associated neurotoxicity syndrome (ICANS), a more severe complication sometimes seen with CAR T therapies.

The ability to limit toxicity while maintaining activity is a key step toward broader application of cell therapies in solid tumors.

Targeting mesothelin across tumor types

SynKIR-110 targets mesothelin, a protein expressed on the surface of several solid tumors but largely absent from normal tissues. This makes it an attractive target for immunotherapy, particularly in cancers such as ovarian cancer and mesothelioma, where treatment options are limited.

The trial results indicate that the therapy’s activity is not confined to a single tumor type, raising the possibility of broader applicability across mesothelin-expressing cancers.

Expanding CAR T into solid tumors

The findings come amid growing efforts to adapt CAR T technology for solid tumors. While the approach has revolutionized hematologic malignancies, solid tumors present additional challenges, including immunosuppressive microenvironments, physical barriers to T cell infiltration, and antigen heterogeneity.

Researchers are exploring multiple strategies to address these barriers, including improved targeting, combination therapies, and next-generation receptor designs such as KIR-CAR.

As noted by CAR T pioneer Carl June, MD, advancing cellular therapies into solid tumors remains a central goal for the field.

Looking ahead

The Phase I study is ongoing, with plans to enroll up to 42 patients and identify the maximum tolerated dose before advancing to a Phase II trial. Early data indicate that CAR T cell expansion in the blood increases with dose, suggesting that higher doses may further enhance efficacy.

While still preliminary, the results highlight the potential of multi-chain CAR designs to address one of the most persistent challenges in cell therapy: maintaining durable activity without excessive toxicity.

If confirmed in larger studies, KIR-CAR therapies could represent a new generation of engineered immune cells, ones that more closely mimic natural immune regulation while retaining the precision of targeted cancer therapy.

For now, the data offer an encouraging signal that the next wave of CAR T innovation may finally extend the reach of cell therapy into solid tumors, where the need remains greatest.

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