The review, authored by Erika P. Plata-Menchaca of the Universitat Autònoma de Barcelona and Hamad Medical Corporation in Doha, and Enrique Hernández-Jiménez of Loop Diagnostics and the University of Barcelona, takes an unusual angle. Instead of ranking biomarkers by diagnostic accuracy or area under the receiver operating characteristic curve, the authors organize candidate technologies by their regulatory status, intended clinical use, sample type, turnaround time and workflow compatibility. The framing follows the 2026 Surviving Sepsis Campaign guidelines, which emphasize early clinical recognition with validated scores, sensible diagnostic strategies and responsible antimicrobial use and de-escalation. A biomarker, they argue, should be judged by whether it can support a concrete decision, whether to admit, escalate, start or stop antibiotics, or monitor more intensively, within the sepsis pathway.

The starting point is the familiar panel of conventional soluble markers. Procalcitonin, C-reactive protein, interleukin-6 and lactate are widely available, analytically standardized and compatible with routine laboratory workflows, and procalcitonin in particular has accumulated regulatory credentials, with multiple CE-marked assays in Europe and several FDA-cleared platforms in the United States supporting antibiotic initiation or discontinuation claims in specific populations. Lactate, although not specific to sepsis, remains central to severity assessment and shock recognition. The weakness of this entire class is biological non-specificity: CRP and interleukin-6 reflect inflammation in general, and procalcitonin concentrations are confounded by surgery, trauma, renal dysfunction, sampling time and non-infectious inflammation. These markers are useful components of assessment, the authors conclude, but they cannot capture the host-response complexity embedded in the Sepsis-3 definition of the syndrome.

A second generation of soluble and hematological markers aims to sharpen that picture. Presepsin, a soluble fragment of the innate immune receptor CD14, and mid-regional proadrenomedullin, a marker of endothelial dysfunction and vascular stress, both performed well in a meta-analysis of adult sepsis diagnostics, with proadrenomedullin slightly ahead. In practice, presepsin is framed as an infection and sepsis support marker available for near-patient testing in Europe on a dedicated chemiluminescent platform, while proadrenomedullin is more compelling for severity, deterioration risk and level-of-care decisions. Pancreatic stone protein has gone further down the regulatory road: the FDA cleared the IVD CAPSULE PSP assay on the abioSCOPE nanofluidic system in 2024 as an aid in early detection of sepsis in high-risk adult ICU patients, and it is also certified under the EU In Vitro Diagnostic Regulation. Monocyte distribution width, a measure of monocyte shape variability generated automatically by Beckman Coulter hematology analyzers, illustrates yet another implementation model, embedding a sepsis screening signal directly into the routine complete blood count for adult emergency department patients.

The most conceptually significant shift, however, is toward molecular and cellular host-response diagnostics that classify the patient’s biological state rather than detecting a pathogen or a single inflammatory protein. SeptiCyte RAPID, an FDA-cleared RT-qPCR assay running on the Biocartis Idylla cartridge platform, measures a two-gene expression signature involving PLAC8 and PLA2G7 to help distinguish infection-positive sepsis from infection-negative systemic inflammation in ICU patients on their first day of admission. TriVerity, from Inflammatix, extends the logic with a 29-transcript host-response signature read by automated RT-LAMP on PAXgene whole blood, designed to differentiate bacterial from viral from non-infectious illness and to estimate the likelihood of mechanical ventilation, vasopressors or renal replacement therapy within seven days in adult emergency patients. IntelliSep, from Cytovale, takes a biophysical route, using deformability cytometry to measure the mechanical properties of activated leukocytes and stratify emergency department patients by risk of sepsis with organ dysfunction within three days.

A further layer comes from functional immune assays, which measure what immune cells can actually do after stimulation rather than merely how much of a protein they are producing at baseline. Endotoxin tolerance, the blunting of leukocyte responsiveness to a lipopolysaccharide challenge after prior inflammatory stress, is a well-established model of immune reprogramming in sepsis, and studies of monocyte HLA-DR expression and ex vivo tumor necrosis factor-alpha responses support its clinical relevance. In a 2024 study, patients with positive blood cultures produced significantly less TNF-alpha after LPS stimulation than culture-negative patients, linking bacteremia-associated sepsis to functional innate immune suppression. That biology now underpins SeptiLoop, a CE-marked Class C near-patient test under the EU IVDR in which heparinized whole blood is stimulated with LPS and TNF-alpha is detected by lateral flow, identifying patients at risk of induced immunosuppression during suspected bacterial bloodstream infection. The review notes transparently that one of its co-authors is the founder of the company developing this test, and that it was assessed under the same descriptive criteria as every competing technology.

Artificial intelligence adds a complementary strategy: rather than relying on any single analyte, machine-learning models integrate many weakly informative signals, from vital signs and demographics to routine laboratory values and sepsis biomarkers, into risk scores. The regulated exemplar is the Sepsis ImmunoScore, an FDA-authorized software-as-a-medical-device that combines up to 22 electronic health record inputs, including procalcitonin, CRP and lactate, to assess the presence of or progression to sepsis within 24 hours in adults being evaluated for suspected sepsis. The authors caution, however, that AI is not a substitute for validated biological measurement. Its value depends on representative training data, transportability between institutions, calibration, handling of missing data, explainability, avoidance of alert fatigue, and, crucially, prospective evidence that model-guided actions improve outcomes. The most plausible future, they suggest, pairs regulated biomarkers supplying reproducible biological signals with AI integrating them into clinical context.

Underlying the entire review is a persistent translational gap. A molecule can be biologically plausible and statistically associated with sepsis yet still lack a regulated product, a defined intended-use population, validated decision thresholds, workflow compatibility, or any evidence that acting on the result improves outcomes. The regulatory landscape is also tightening and fragmenting. The EU IVDR has raised the evidentiary and quality bar for in vitro diagnostics, particularly higher-risk and near-patient assays, and the first four modules of the EUDAMED database became mandatory on 28 May 2026, increasing transparency across Europe. Regulatory status, the authors stress, must always be reported by jurisdiction and intended use: CE-IVD certification, FDA 510(k) clearance and other national approvals do not imply identical claims, populations or workflows, and the same biological signal may serve very different decisions, from early recognition and prognosis to antimicrobial de-escalation and immune phenotyping.

The authors are candid about their own limitations. The review involved no formal risk-of-bias assessment, evidence grading or quantitative meta-analysis, and comparisons across technologies are complicated by heterogeneous populations, sepsis definitions, reference standards and endpoints. Regulatory status is jurisdiction- and product-specific and changes over time, and many emerging diagnostics and AI tools still lack prospective studies demonstrating an impact on patient outcomes. Even so, the direction of travel is clear. Sepsis diagnostics are moving beyond isolated inflammatory analytes toward integrated, multi-layered host-response testing, combining soluble severity markers, hematology-derived parameters, transcriptomic classifiers, leukocyte biophysical assays and functional immune measurements. The decisive question for each new test is no longer whether its target is associated with sepsis, but whether a certified product, deployed where clinicians actually work, reduces diagnostic uncertainty at the moments when that uncertainty determines treatment, resource use and survival.

Subject of Research: Translation of sepsis biomarkers from discovery into regulated in vitro diagnostic tests

Article Title: From sepsis biomarker discovery to regulated in vitro diagnostics: evidence, certification status and implementation gaps

Article References: From sepsis biomarker discovery to regulated in vitro diagnostics: evidence, certification status and implementation gaps. (n.d.). https://doi.org/10.3389/fmedt.2026.1916860

Image Credits: AI Generated

DOI: 10.3389/fmedt.2026.1916860

Keywords: sepsis, biomarkers, in vitro diagnostics, procalcitonin, host response, FDA clearance, EU IVDR, transcriptomics, immune monitoring, artificial intelligence, antimicrobial stewardship, point-of-care testing

The study, published in the journal Clinical Infectious Diseases, was supported through long-standing funding from the National Institutes of Health and describes the analytical and clinical performance data that underpinned the FDA clearance of the assay for use in adults with suspected invasive aspergillosis. Sean X. Zhang, M.D., Ph.D., the senior study author, an associate professor of pathology and director of the Medical Mycology Laboratory at Johns Hopkins Medicine, emphasized what is at stake in the speed of diagnosis. “Having an early diagnosis is critical; it can initiate appropriate and timely treatment to help prevent disease progression and increase the odds of survival,” Zhang said in the announcement accompanying the publication.

The clinical problem the test addresses is stark. Invasive aspergillosis is generally rare in people with healthy immune systems, but its prevalence within vulnerable populations is substantial. Studies have estimated that the infection develops in 5 to 15 percent of patients with acute myeloid leukemia, or in those receiving bone marrow transplants for conditions such as sickle cell disease. It has also been identified in 5 to 20 percent of patients admitted to the intensive care unit with severe influenza or COVID-19, a category of cases that gained renewed attention during the pandemic. Despite the availability of antifungal treatment, up to half of some high-risk populations may die from the infection, a mortality figure that reflects both the aggressiveness of the disease and the difficulty of diagnosing it in time.

Historically, establishing a diagnosis of invasive aspergillosis has required a laborious combination of evidence. Clinicians have relied on chest imaging, blood tests, respiratory samples obtained during bronchoscopy and, in some cases, tissue biopsy. Several of these approaches are invasive, demanding procedures that can be risky for patients who are already profoundly ill, neutropenic or recovering from major transplantation. Even after such workups, uncertainty often remains, and antifungal therapy may be started empirically in patients who ultimately turn out not to have the infection, exposing them to toxicity, drug interactions and unnecessary cost. The newly cleared assay takes a different approach: rather than requiring bronchoscopic or tissue sampling, it directly detects Aspergillus antigens in urine and can return a laboratory result within several hours, using a specimen that can be collected noninvasively at the bedside. The test is intended to be used alongside clinical findings, imaging and other laboratory tests, not to replace them.

The core of the publication is a rigorous validation study of the assay’s ability to detect Aspergillus galactofuranose-containing antigens, proteins that signal the body’s response to this infection. The investigators analyzed frozen urine samples from 290 study participants who had been enrolled in studies in the United States and Belgium at various times between 2009 and 2022. Of these participants, 50 had a confirmed case of invasive aspergillosis and 240 served as controls, giving the analysis a substantial body of true-positive and true-negative material against which the test could be measured. The frozen-sample design allowed the investigators to evaluate the assay blindly, on specimens collected years before the test existed, which is a meaningful advantage in a disease where prospective enrollment of large numbers of confirmed cases is difficult.

The performance figures reported from that retrospective cohort are striking. Among the 50 participants with confirmed invasive aspergillosis, the urine test correctly identified 46 cases, a sensitivity of 92 percent; only four cases produced false negative results. On the negative side, the test correctly identified 218 of 249 samples as negative, a specificity of 88 percent. To guard against site-specific artifacts, the urine samples were tested at laboratories in Baltimore, Maryland; Pittsburgh, Pennsylvania; and Raleigh, North Carolina, providing a multi-center assessment of reproducibility. For a noninvasive test that yields results within hours, those operating characteristics compare favorably with the diagnostic pathways it is designed to complement, which often involve invasive procedures and delays of days.

Retrospective accuracy alone does not establish a test’s usefulness in the messy reality of clinical medicine, where patients suspected of infection frequently turn out to have something else. To address this, the investigators conducted a second phase of research examining how the assay performs in real time among people suspected of having invasive aspergillosis who were receiving care at The Johns Hopkins Hospital for conditions such as blood cancer or autoimmune diseases between January 2023 and February 2024. Of the 210 participants suspected of having the infection who provided samples, 168 were eligible for analysis, and 171 fresh urine samples were analyzed in real time in the hospital laboratory. In this prospective component, a small portion of the participants had confirmed results: seven confirmed positive and 39 confirmed negative. Against those confirmed outcomes, the test correctly identified six of the seven positive cases, or 86 percent, and 35 of the 39 negative cases, or 90 percent.

Perhaps the most clinically revealing finding came from the large group of patients in whom the diagnosis remained uncertain. Among the 210 people suspected of having invasive aspergillosis, about half lacked a confirmed diagnosis, a proportion that captures the everyday diagnostic ambiguity of the disease. Yet among those suspected cases without confirmation, the urine test produced a positive result in roughly one in four. The researchers say this pattern demonstrates the benefit of having such a diagnostic tool available in a hospital setting, because it can begin to stratify an uncertain population into those with evidence of infection and those in whom alternative explanations should be pursued, all without subjecting patients to additional invasive procedures.

Nitipong Permpalung, M.D., M.P.H., director of mycology research and associate director for clinical trials at the Johns Hopkins Transplant Research Center, framed the value of the test in terms of the clinical decision-making it enables. “For patients with blood cancers or stem cell transplants, the hardest part is often the gap between suspecting invasive aspergillosis and having enough evidence to act,” Permpalung said. “This urine test is not a stand-alone answer, but it can provide another piece of evidence quickly and noninvasively, which could help us move faster for patients most likely to benefit from treatment while avoiding unnecessary antifungal exposure when infection is less likely.” That dual promise, faster treatment for true infections and less gratuitous antifungal use for everyone else, is precisely the calculus that determines outcomes and toxicity in immunocompromised wards.

The work is not finished. The investigators are currently studying how the assay performs when incorporated into routine clinical care, and whether it may provide value in other high-risk settings, including among immunocompromised patients evaluated for fungal complications following respiratory viral infections, a population that grew in prominence during the influenza and COVID-19 pandemics. The research also aligns with global priorities set by the World Health Organization, which in 2022 named Aspergillus fumigatus to its list of critical-priority fungal pathogens as part of its program to better diagnose, treat and prevent invasive aspergillosis. The published study, titled “Performance of the Urinary MycoMEIA Aspergillus Assay as an Aid to Diagnose Invasive Aspergillosis,” appears in Clinical Infectious Diseases with the DOI 10.1093/cid/ciag522. Additional authors include Irina Baburina, Kieren Marr, Yuri Vanbiervliet, Chiung-Yu Huang, Robina Aerts, Patricia Marques, Andrew Shorr, M. Hong Nguyen, Binghua Hao, John Wingard and Johan Maertens. The study was funded by Pearl Diagnostics, Inc., and NIH grant R44AI157572. Disclosures note that Kieren Marr started Pearl Diagnostics in 2014 and is a shareholder of the company, and that several authors, including Permpalung and Zhang, have received consulting income or sponsored research support from Pearl Diagnostics and a range of other diagnostics and therapeutics companies. For a disease that kills up to half of some high-risk groups, the arrival of a validated, hours-fast, urine-based diagnostic marks one of the most consequential additions to the invasive aspergillosis toolkit in years.

Subject of Research: Clinical validation of a rapid urine-based antigen assay for diagnosing invasive aspergillosis

Article Title: Johns Hopkins Medicine researchers publish clinical data for rapid diagnostic urine test to detect invasive aspergillosis

Article References: Johns Hopkins Medicine researchers publish clinical data for rapid diagnostic urine test to detect invasive aspergillosis. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: invasive aspergillosis, Aspergillus, urine antigen test, FDA clearance, diagnostic assay, galactofuranose antigens, immunocompromised patients, bone marrow transplant, Clinical Infectious Diseases, Johns Hopkins Medicine, antifungal therapy, WHO fungal priority list

The significance of the moment is hard to overstate. Sleep is a quantifiable and clinically rich physiological state, making it a natural target for continuous health monitoring ever since wrist-worn actigraphy was first introduced by Kripke and colleagues in 1978. Yet while wearable hardware has evolved at a breakneck pace, the standards for validating these technologies have lagged far behind. Experts have increasingly called for formal guidelines governing how consumer devices that deliver diagnostic assessments and medical advice should be tested. Adoption, meanwhile, has already crossed a tipping point: more than 40 percent of US adults now use wearable devices. As photoplethysmography and oximetry sensors mature, these gadgets are no longer merely counting steps but making claims once reserved for medical equipment.

The study by Alavi and colleagues put the Galaxy Watch through an unusually rigorous test. The investigators enrolled 147 participants and gathered data on two separate nights, comparing the watch’s estimated apnea-hypopnea index against full in-lab polysomnography, the gold standard for sleep apnea diagnosis. The two monitored nights were separated by four to ten nights of at-home recording, a design that aligned directly with the FDA-cleared two-night decision framework while also capturing the natural night-to-night variability of the disorder. The researchers benchmarked the watch not only against conventional respiratory event frequency metrics but also against hypoxic burden, an emerging measure of the cumulative oxygen deprivation a patient experiences during sleep.

The headline numbers are striking. Against the polysomnography-derived apnea-hypopnea index scored at a 4 percent oxygen desaturation threshold, the watch’s estimate achieved an area under the receiver operating characteristic curve of 0.94, with a correlation of 0.87, its strongest diagnostic performance. Even more impressive, among participants classified into the high-risk hypoxic burden stratum, the algorithm achieved 100 percent sensitivity and 100 percent specificity. This suggests that optical photoplethysmography and wrist oximetry are especially discriminative when the cumulative hypoxemic stimulus is large. The performance profile aligns with a hypoxia-based screening approach and hints at reduced discriminatory power for milder disease, where arousals rather than oxygen drops dominate the pathology.

Equally notable was the study’s attention to a well-known weakness of optical sensing: skin pigmentation. Pulse oximeters measure light absorption through tissue, and darker skin tones have historically degraded their accuracy. The investigators conducted structured subgroup analyses across sex, body mass index, age, ethnicity, and objectively measured skin pigmentation. They found consistent sensitivity above 91 percent and consistent specificity across darker skin tones, addressing a vulnerability that has plagued optical pulse oximetry for generations and that regulators have scrutinized intensely in recent years.

But the commentary authors identify serious caveats that temper the enthusiasm. The study population was enriched for individuals with either a prior diagnosis of moderate-to-severe obstructive sleep apnea or a high pre-test probability, defined by a STOP-Bang score of 3 or greater. Of the 147 participants who completed both laboratory nights, 97 had moderate-to-severe sleep apnea on both nights, while only 29 had an apnea-hypopnea index below 15 on both nights. This spectrum bias artificially inflates positive predictive values, which exceeded 95 percent in the study. In a low-prevalence general screening population, the false positive rate would be substantially higher, a statistical reality that could overwhelm sleep clinics with unnecessary referrals.

The raw performance figures at the manufacturer’s default threshold tell a more complicated story. At an estimated apnea-hypopnea index cutoff of 15 events per hour, the device showed high sensitivity of 94.1 percent but a notably modest specificity of only 66.7 percent against the 4 percent oxygen desaturation index, and 65.8 percent against the standard apnea-hypopnea index. That figure stands in contrast to the 87.7 percent specificity reported in the FDA De Novo authorization summary. When the investigators shifted the cutoff to a cohort-optimized threshold of 25.95 events per hour, specificity rose to 94.9 percent but sensitivity fell to 82.4 percent. In other words, the device can be tuned to catch most cases or to avoid most false alarms, but not both simultaneously, and clinicians deploying it must understand exactly where that trade-off sits.

Real-world data quality posed another problem. Among the 147 participants who completed both in-lab polysomnography sessions, 57 lacked valid watch data on one or both laboratory nights because of poor signal quality, motion artifact, or inadequate wrist coupling, an invalidation rate of 38.8 percent during attended studies. The researchers supplemented missing data with home recordings for research purposes, but unwitnessed home recordings remain susceptible to unmeasured confounders such as positional therapy, alcohol consumption, sleep fragmentation, or undiagnosed central apnea events. A wearable that fails to produce usable data in nearly four out of ten supervised sessions highlights the ongoing engineering challenge of sensor displacement and optical signal loss in wrist-worn consumer hardware.

The study also excluded patients with significant cardiac disease, chronic pulmonary disease, movement disorders, and comorbid sleep disorders. These are precisely the comorbid conditions that are common among patients referred for sleep evaluation, meaning the algorithm’s performance in multimorbid populations remains unproven. The US Preventive Services Task Force, moreover, does not currently support screening for obstructive sleep apnea in the absence of symptoms, citing insufficient evidence of screening accuracy and inconsistent evidence on health outcomes. Any wearable-based screening program would therefore operate in a gray zone of preventive medicine, generating findings that guidelines do not yet know how to handle.

The practical implications for clinicians are concrete. Used as a sole screening tool at the default 15 events per hour threshold, the watch would generate a significant number of false positives, burdening downstream sleep clinic resources and confirmatory diagnostic pathways. Confirmatory testing with polysomnography or home sleep apnea testing would still be required before initiating therapy. Yet the commentary authors see genuine value in the device’s ability to identify high-risk individuals with significant hypoxic burden, positioning it as an accessible triage entry point rather than a diagnostic endpoint. In their view, the work by Alavi and colleagues provides a reasonable roadmap for validating emerging wearable devices and algorithms, and industry’s willingness to seek FDA approval for clinical claims is itself an encouraging development. Deployment, they conclude, would still require careful appraisal of positive and negative predictive values within each specific population and clinical setting. The smartwatch has crossed a threshold, but it has not yet arrived at its destination.

Subject of Research: Validation of a consumer smartwatch algorithm for detecting moderate-to-severe obstructive sleep apnea

Article Title: A smart watch crosses the threshold into clinical practice—or not quite yet?

Article References: Khayat, R. N., & Floyd, M. S. (2026). A smart watch crosses the threshold into clinical practice—or not quite yet?. Journal of Clinical Sleep Medicine, 22(1), Article 181. https://doi.org/10.1007/s44470-026-00195-4

Image Credits: AI Generated

DOI: 10.1007/s44470-026-00195-4

Keywords: wearable technology, obstructive sleep apnea, smartwatch, photoplethysmography, sleep medicine, FDA clearance, hypoxic burden, polysomnography, diagnostic validation, screening, oximetry, skin pigmentation

The therapy belongs to a class of treatments known as CAR T-cell immunotherapy. The process begins with the collection of a patient’s own T cells, the immune system’s specialized killers. In the laboratory, those cells are genetically modified so that they carry engineered receptors capable of recognizing and binding to specific molecules on the surface of cancer cells. Once reprogrammed, the cells are expanded into large numbers and returned to the patient, where they circulate, seek out their targets and attack. The technique has already produced striking results in certain blood cancers, including leukemia and lymphoma, where engineered immune cells have driven durable remissions in patients who had exhausted every other option.

Translating that success to solid tumors such as colorectal cancer has proved far more difficult. Solid tumors are physically dense, immunologically hostile environments that engineered cells struggle to infiltrate and survive in. They deploy molecular defenses that suppress or redirect immune attacks, and they present a fundamental targeting problem: researchers must find a molecule that is abundant on cancer cells but scarce on healthy tissue, so that the therapy attacks the tumor without destroying vital organs. That targeting challenge has been one of the central obstacles holding back CAR T-cell therapy for the many cancers that form solid masses rather than circulating freely in the blood.

The CU Anschutz team believes it has found a way around that obstacle by aiming at two targets at once. The first is B7-H3, a protein found on the surface of most colorectal tumors and, importantly, on a wide range of other cancers as well. Researchers at several institutions have been investigating B7-H3 as a potential cancer target precisely because of its broad presence across tumor types. The second target is IL-8, a signaling protein that helps promote tumor growth, inflammation and the spread of cancer through the body. By simultaneously targeting B7-H3 and the IL-8 pathway, the engineered cells are designed to strike both the tumor itself and one of the biological systems it uses to grow and evade immune destruction. The researchers hope that this two-pronged strategy will give the engineered cells a better chance of overcoming the defenses that have limited earlier attempts to treat solid tumors with CAR T-cell therapy.

The dual-target design also reflects a deliberate strategic choice about which patients the therapy could eventually serve. Michael Verneris, MD, professor of pediatric oncology at CU Anschutz and program co-leader of Tumor-Host Interactions at the CU Anschutz Cancer Center, said the team wanted to move away from highly narrow approaches. “This is a very different way of thinking about how we treat cancer,” Verneris said. “We wanted to find targets that are present across many different cancers rather than developing a therapy that would only apply to a small number of patients.” If the trial demonstrates that the approach is safe and effective, the researchers say it could eventually be tested against other cancers in which these pathways play a role, including some breast, lung and ovarian cancers.

Christopher Lieu, MD, professor of medical oncology at CU Anschutz and associate director of clinical research at the CU Anschutz Cancer Center, is leading the trial. He framed the therapy as a potential alternative to the blunt instruments of conventional treatment. “Chemotherapy extends survival and helps cure people,” Lieu said. “At the same time, it’s like dropping an unguided bomb on a disease. Maybe you hit your target, but you are going to do a lot of collateral damage.” He is hoping the therapy, which has proven effective in animal models, will produce far longer-lasting results than current options typically deliver. “Immunotherapy gives us the opportunity to direct the immune system toward the cancer and potentially produce a much more durable response,” he said. The goal, he added, is not measured in months but in years.

The urgency behind the trial is underscored by troubling epidemiological trends. Colorectal cancer is increasingly affecting younger adults, with rates among people under 45 rising substantially over the past several decades while researchers continue to investigate the reasons behind the shift. For patients whose disease advances despite standard therapies, options narrow rapidly. Currently, only a small percentage of patients with colorectal and other gastrointestinal cancers qualify for certain forms of immunotherapy, because those treatments depend on specific tumor biomarkers that many patients do not have. Because B7-H3 is present in a much larger proportion of colorectal cancers, the researchers hope their approach could ultimately be applicable to a far broader patient population. “Given the number of patients we are seeing, we need new approaches,” Lieu said. But he and his colleagues are careful to note that the first step is determining whether the therapy is safe in people and whether it can effectively attack cancer in the human body, as it has in animal models.

The path from concept to clinical trial also highlights the structural advantages of the CU Anschutz campus, which brings together the university’s health professional schools, Children’s Hospital Colorado, UCHealth University of Colorado Hospital and the Gates Biomanufacturing Facility within easy walking distance of one another. The experimental cells for the trial will be manufactured at the Gates Biomanufacturing Facility, meaning the entire pipeline, from basic research to cell production to patient treatment, exists on a single campus. “The whole spectrum is right here,” Verneris said. “If we didn’t have the Gates Institute, we wouldn’t be able to make our own cells. This could have remained an interesting idea. Instead, it has become a clinical trial that could have a real impact on patients.” Philanthropic support has been essential to reaching this point, Verneris noted, because trials of this kind are expensive and private donations made it possible to move the therapy from the laboratory into patients. “We are incredibly grateful to the donors who have helped make this possible,” he said.

For the patients who enroll, the trial represents something that advanced colorectal cancer currently offers in short supply: a chance at a treatment designed to last. If the engineered cells can safely navigate the hostile terrain of solid tumors and dismantle the pathways that colorectal cancers use to grow and spread, the trial could open a new front against one of the most common and increasingly prevalent cancers, and potentially against several others beyond it. The FDA’s clearance now allows that hypothesis to be tested in the place it matters most, in the bodies of the patients the therapy was designed for.

Subject of Research: A first-in-human clinical trial of dual-target CAR T-cell immunotherapy for advanced colorectal cancer

Article Title: FDA clears CU Anschutz clinical trial using engineered immune cells to fight colorectal cancer

Article References: FDA clears CU Anschutz clinical trial using engineered immune cells to fight colorectal cancer. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: CAR T-cell therapy, colorectal cancer, FDA clearance, clinical trial, immunotherapy, B7-H3, IL-8, solid tumors, CU Anschutz, pediatric cancer, engineered immune cells, Gates Biomanufacturing Facility