Obecabtagene autoleucel, a CD19-directed autologous CAR T-cell therapy, demonstrated significantly superior efficacy compared with standard treatments for relapsed or refractory B-cell acute lymphoblastic leukemia in adults. The propensity score-matched analysis of the phase 1b/2 FELIX trial (107 patients) showed overall remission rates of 67.3% versus 51.4% in matched controls receiving blinatumomab, inotuzumab ozogamicin, or chemotherapy. In the modified intent-to-treat population, remission rates reached 79.8% compared with 54.8% in controls. Median overall survival favored CAR T-cell therapy at 15.1 months with transplant censoring versus 7.0 months with standard care, while median event-free survival was 9.8 months versus 2.5 months. Safety profiles remained comparable between groups. These results, published in Leukemia, suggest obecabtagene autoleucel addresses significant clinical needs in this high-risk population where outcomes with conventional therapies remain poor.

This Frontiers in Immunology review examines in vivo CAR T-cell generation, a promising approach that engineers T cells directly within the patient's body rather than through traditional ex vivo manufacturing. Authored by Huo, Yao, and Kong, the article evaluates emerging delivery platforms essential for clinical translation, particularly lentiviral vectors and lipid nanoparticles, which serve as critical vehicles for introducing CAR-encoding genetic material into patient lymphocytes. The review synthesizes current clinical progress in this field while identifying significant translational barriers that must be overcome for widespread therapeutic adoption. By analyzing both established and novel gene delivery systems, the authors provide comprehensive insights into optimizing in vivo CAR T-cell therapy's efficacy and safety. This work matters substantially because in vivo approaches could circumvent manufacturing bottlenecks, reduce costs, and accelerate treatment availability for cancer patients, while the identified barriers inform future research priorities aimed at realizing this technology's full clinical potential.

Complicated urinary tract infections (cUTIs) present escalating clinical challenges as antimicrobial resistance increasingly compromises treatment efficacy. These infections involve resistant uropathogens, recurrent episodes, urinary tract abnormalities, catheterization, and comorbidities that drive poor outcomes and treatment failures. Recent advances have deepened understanding of molecular resistance mechanisms, bacterial adaptation, biofilm formation, and host-pathogen interactions, while rapid diagnostics and genomic surveillance technologies promise more targeted antimicrobial selection. However, significant implementation gaps persist between research discoveries and clinical practice. Critical unresolved questions include optimal definitions of cUTIs, ideal therapy duration and routes, combination treatment protocols, and diagnostic stewardship strategies to minimize unnecessary antimicrobial exposure. This Research Topic addresses these complexities by examining biological, diagnostic, and therapeutic dimensions of resistant cUTIs. It seeks studies investigating resistance emergence and transmission, factors contributing to treatment failure, and approaches enhancing diagnostic accuracy and antimicrobial decision-making. The initiative also explores innovative non-traditional therapies, including bacteriophage-based interventions, alongside conventional antimicrobials. By integrating clinical microbiology, infectious disease, and urology perspectives, this collaborative effort aims to establish evidence-based management strategies for patients with resistant uropathogens.

# Professional Summary This comprehensive review examines the immunological mechanisms distinguishing "cold" tumors, characterized by low immune infiltration and poor immunotherapy response, from "hot" tumors with robust anti-tumor immunity. The authors analyze dysregulation within the cancer-immunity cycle—the sequential steps through which the immune system recognizes and eliminates cancer cells—identifying key checkpoints where this cycle breaks down in cold tumors. The article explores how immunosuppressive factors, tumor microenvironment characteristics, and immune evasion strategies contribute to this dichotomy. Critically, the review evaluates emerging nanotechnology-driven therapeutic approaches designed to convert cold tumors into immunologically active hot tumors. These nano-based strategies include targeted drug delivery systems, nanoparticle-mediated immune activation, and combination therapies enhancing checkpoint inhibitor efficacy. Understanding these immunological determinants and developing effective interventions matters significantly for improving outcomes in patients with treatment-resistant cancers and expanding immunotherapy applicability beyond currently responsive tumor types.

Researchers have developed an innovative "micro-bladder" model to investigate why urinary tract infections persist despite antibiotic treatment. This flowing tissue-engineering system mimics the dynamic conditions within the human bladder, revealing that bacteria survive in ways standard laboratory susceptibility tests cannot detect. The micro-bladder demonstrates how pathogens evade apparently appropriate antibiotics, explaining the clinical reality faced by millions of patients, particularly women experiencing recurrent UTIs where symptoms return weeks or months after treatment. By simulating actual bladder physiology rather than static in vitro conditions, this device provides critical insights into bacterial survival mechanisms and treatment resistance. The findings have significant implications for developing more effective UTI therapies and improving clinical outcomes for patients with chronic infections who currently face incomplete pictures from conventional diagnostic methods.

This comprehensive analysis examines T-cell redirecting therapies as emerging treatment approaches for lung cancer. The research reviews clinical trial data on three primary therapeutic modalities: bispecific T-cell engagers (BiTEs), chimeric antigen receptor T (CAR-T) cell therapy, and TCR-engineered T cells, alongside tumor-infiltrating lymphocyte (TIL) strategies. These immunotherapies work by redirecting and activating patients' own T cells to recognize and eliminate cancer cells. The study synthesizes evidence from multiple clinical trials to evaluate the efficacy, safety profiles, and clinical outcomes of these approaches in lung cancer patients. This analysis matters significantly as T-cell redirecting therapies represent a paradigm shift in oncology, offering potential alternatives or complements to conventional treatments. Understanding their performance across diverse trial settings provides critical insights for clinicians and researchers evaluating treatment options and informs future development of optimized immunotherapeutic strategies for this disease.

Cancer treatment is increasingly shifting toward personalized approaches that harness the immune system's power. A landmark clinical trial demonstrates that combining Moderna and Merck's experimental mRNA vaccine intismeran with Merck's established immunotherapy pembrolizumab (Keytruda) significantly outperforms Keytruda alone in treating melanoma. The study enrolled 1,137 patients with stage 2 to 4 melanoma who underwent surgery, then received either the combination therapy or Keytruda monotherapy for over a year. Patients receiving both treatments experienced longer recurrence-free survival and fewer instances of cancer spread. Intismeran represents a novel autogene therapy that analyzes individual tumor mutations, generates personalized mRNA sequences encoding those mutations, and administers them as a therapeutic vaccine to train the immune system to recognize cancer cells. The mRNA platform's key advantage lies in its rapid sequence generation capability—achievable within weeks—enabling scalable personalized cancer treatment. While Keytruda works by exposing hidden cancer cells to immune detection, intismeran teaches the immune system to identify tumor-specific mutations. Though intismeran remains unapproved, these results suggest that combining personalized mRNA vaccines with checkpoint inhibitors represents a promising therapeutic strategy for melanoma management.

The Neo-CheckRay trial, a randomized Phase 2 study published in Nature Medicine, investigated whether radiation could enhance immunotherapy sensitivity in estrogen receptor-positive, HER2-negative breast cancer, a traditionally immune-cold tumor type with limited immunotherapy benefit. Researchers led by Alex De Caluwé evaluated neoadjuvant immune-modulating stereotactic body radiation therapy (iSBRT) combined with chemotherapy, with or without the PD-L1 inhibitor durvalumab and CD73 inhibitor oleclumab, in women with high-risk early-stage disease. While the trial did not achieve its primary endpoint of significantly improving residual cancer burden 0/1 response rates, it revealed a counterintuitive finding: the greatest benefit from checkpoint inhibition appeared in PD-L1-negative tumors, a subgroup conventionally considered less responsive to immunotherapy. This contrasts with prior Phase 3 trials like KEYNOTE-756 and CheckMate 7FL, which showed modest pCR improvements with standard immune checkpoint blockade. Neo-CheckRay's novel approach attempted to reprogram the tumor microenvironment through radiation-induced immune modulation, addressing the fundamental challenge of immune suppression in ER-positive/HER2-negative disease and potentially redefining patient selection for immunotherapy in this population.

Merck and Moderna announced positive Phase 3 results from the INTerpath-001 trial evaluating intismeran autogene, a personalized neoantigen immunotherapy, combined with Merck's KEYTRUDA (pembrolizumab) in patients with completely resected stage IIB-IV melanoma. The combination met both primary endpoints, demonstrating statistically significant improvements in recurrence-free survival and distant metastasis-free survival compared to KEYTRUDA monotherapy. Intismeran autogene is a therapeutic cancer vaccine designed to activate the immune system against patient-specific tumor mutations. The trial involved melanoma patients at high risk of recurrence following surgical resection. These results represent a significant advancement in adjuvant melanoma treatment, potentially establishing the personalized vaccine plus checkpoint inhibitor approach as a new standard of care. The positive findings underscore the therapeutic potential of combining individualized neoantigen vaccines with immunotherapy, offering promise for improving long-term outcomes in high-risk melanoma patients and potentially informing strategies in other cancer types.

Le changement climatique est aujourd’hui reconnu comme une menace majeure pour la santé publique. Paradoxalement, le secteur de la santé, conçu pour soigner et prévenir les maladies, contribue lui-même à ce problème : il représente environ 5 % des émissions mondiales de gaz à effet de serre, avec des chiffres pouvant atteindre 10 % dans certains pays industrialisés. Parmi les activités médicales, l’imagerie occupe une place importante : on estime qu’elle contribue à près de 10 % de l’empreinte carbone des systèmes de santé.

For years, the idea of a cancer vaccine has sounded almost contradictory. However, the latest Phase 3 results from Moderna and Merck have pushed the personalized mRNA cancer vaccine concept much closer to clinical reality. Vaccines are supposed to prevent infectious diseases. Cancer, on the other hand, develops from our own cells. How could we vaccinate the immune system against something that technically belongs to us? That question became much more interesting this week.

“Phage therapy is promising and may eventually be a big part of treating infections in the future,” Vance Fowler, MD, a professor of medicine in the division of infectious diseases at Duke University School of Medicine, wrote in an email. “The challenge is that right now none of us seem to have sorted out how to use it, how to administer it, or even how to figure out if the bacteria infecting the patient we are trying to treat are susceptible to the phages used to treat them.”

Triple-negative breast cancer (TNBC) management increasingly relies on biomarker testing, yet treatment selection depends on relatively few validated markers. While pembrolizumab, a PD-1 inhibitor, gained FDA approval in 2021 for high-risk early-stage TNBC combined with chemotherapy regardless of PD-L1 status—supported by improved survival data from the KEYNOTE-522 trial—PD-L1 remains imperfect as a predictive biomarker. Its utility varies by disease setting, assay type, and scoring methodology. In metastatic TNBC, only 30-40% of patients achieve the required combined positive score of at least 10 for pembrolizumab eligibility. Alternatives include PARP inhibitors olaparib and talazoparib for patients with germline or somatic BRCA mutations, as well as HER2-targeted therapies. However, microsatellite instability-high and mismatch repair-deficient TNBCs are rare, and most TNBCs fail to meet high tumor mutation burden thresholds. Oncologists stress the need for additional biomarkers to better predict immunotherapy and targeted therapy responses, improving personalized treatment strategies for this aggressive cancer subtype.

Researchers at the Centre for Kidney and Bladder Health, University College London, have developed a novel human 3D micro-bladder model to investigate phage therapy as a treatment for recurrent urinary tract infections caused by uropathogenic Escherichia coli. The study, published in Nature Communications, demonstrates that a cocktail of bacteriophages can effectively eliminate bacteria hidden within bladder wall tissue—so-called "reservoirs"—where conventional antibiotics cannot reach. This addresses a critical clinical challenge: bacteria evade antibiotic treatment by retreating into protected areas, causing frustrating recurrent infections. The micro-bladder model, which incorporates flowing urine to replicate authentic urinary tract conditions, revealed that the bladder microenvironment significantly influences infection dynamics and therapeutic outcomes. With approximately 400 million UTI cases annually and rising antimicrobial resistance threatening treatment efficacy, this research offers promising insights for developing advanced therapeutic strategies. The findings underscore the importance of sophisticated biological models in guiding treatment approaches during the antimicrobial resistance era and suggest phage therapy represents a viable alternative to conventional antibiotics for managing recurrent UTIs.

Researchers have developed a novel immunotherapy approach utilizing extracellular vesicles derived from induced pluripotent stem cell-derived natural killer cells engineered with chimeric antigen receptors (iPSC-derived CAR-NK EVs) to treat non-small cell lung cancer. This innovative strategy addresses a critical gap in cancer therapeutics by leveraging the therapeutic potential of CAR-NK cells while circumventing challenges associated with direct cell administration. The study, authored by Liang and colleagues and published in Frontiers in Immunology, comprehensively examines the scientific evidence supporting this approach, alongside engineering considerations and translational hurdles. A key innovation involves inhalation delivery of these vesicles directly to the lungs, enabling targeted tumor microenvironment engagement while potentially reducing systemic toxicity. The research emphasizes the importance of potency assays for characterizing these extracellular vesicles and ensuring therapeutic efficacy. By combining iPSC-derived cell technology with CAR-NK immunotherapy in an acellular vesicle format, this approach offers significant advantages including reduced immunogenicity, improved scalability, and enhanced bioavailability. The work establishes a foundation for translating this technology toward clinical application while identifying remaining barriers to overcome for successful therapeutic implementation.

The transvenous insertion of implantable pacemaker (PM) and implantable cardioverter defibrillator (ICD) leads was a major milestone in antiarrhythmic therapy with the use of cardiac devices. Indeed, based on data published over the last decade the indications for ICD therapy have further expanded [1,2] while cardiac resynchronization therapy (CRT) through bi-ventricular pacing has significantly improved mortality and quality of life in patients with heart failure and ventricular dyssynchrony [3,4,5]. Unfortunately, this exponential increase in the implantation rate of cardiac devices has been accompanied by a parallel increase in the need for explanting some of those [6]. This has been mainly attributed to the so called “increased total lead exposure time” resulting from the expanding indications for device treatments, the implantation of more leads per patient and the longer average life expectancy of device-recipients [7].

This article is dedicated to CEOs/Founders/start-up teams who are building in the healthcare industry and looking for: increasing their visibility, attracting funds, expanding their network, growing their business. A start-up can access funds through diverse methods, including bootstrapping, angel investors, venture capital, and government grants. Non-dilutive funding allows start-ups to raise capital without surrendering any equity or ownership stakes.

Despite the systemic spread of cancer, the ventricular myocardium is one of the least common sites of metastasis—a phenomenon that remains poorly understood. To examine this, we develop the Multi-organ Invasion Device (MInD), an organ-on-a-chip platform that enables multi-organ culture under flow. Organ compartments are connected in MInD using PermeoTubes—3D-printed porous conduits that support cancer cell intravasation, migration, and extravasation. In dual-organ devices, where highly aggressive breast cancer cells are co-cultured with either hepatic or cardiac tissue, invasion into cardiac tissue is significantly suppressed relative to hepatic co-culture. Importantly, in cardiac–hepatic–cancer tri-culture, the presence of cardiac tissue reduces overall invasion, with cancer cells preferentially migrating toward hepatic compartments. Cytokine profiling and RNA sequencing reveal that cardiac co-culture suppresses cell metastasis and invasion, while inducing immune activation. Overall, this platform presents an approach for uncovering organ-specific drivers of metastasis, accelerating future discovery of metastasis-inhibiting therapies.

La biotech allemande et son allié suisse Roche ont annoncé arrêter l'essai de leur vaccin personnalisé contre le cancer, faute d'efficacité. Ce vaccin à ARN messager, comme celui de Moderna, était testé pour prévenir la rechute dans le cancer colorectal.

At least 24.5 percent of former NFL players who died between 2016 and 2021 had CTE pathology at death, according to a new study. The authors say the rate could be as high as 97.7 percent, depending on how many players whose brains were not examined also had the disease. Among 315 brain donors whose tissue showed CTE, 61.3 percent had dementia diagnosed by study clinicians. That number rose to 90.4 percent for donors with Stage IV CTE. Because CTE can be confirmed only after death, the study cannot determine how common it is among living players.  The findings support continued research on prevention, symptom treatment, and efforts toward new treatments for CTE.