This phase II clinical trial investigates ivermectin combined with the immunotherapeutic monoclonal antibodies balstilimab or pembrolizumab for treating metastatic triple-negative breast cancer. The study evaluates safety, optimal dosing, and efficacy of this combination approach. Immunotherapy agents like balstilimab and pembrolizumab enhance the immune system's capacity to attack cancer cells, while ivermectin may inhibit tumor growth formation. The synergistic combination aims to maximize tumor shrinkage. Secondary endpoints assess objective response rate, progression-free survival, overall survival, duration of response, clinical benefit rate, and patient quality of life using the EORTC QLQ-C30 questionnaire. Eligible participants must be at least eighteen years old with confirmed metastatic triple-negative breast cancer (characterized by negative estrogen and progesterone receptors and HER2-negative status), prior systemic therapy exposure, and adequate organ function. The phase two expansion cohort requires PD-L1 negative status. This trial addresses a significant unmet need in triple-negative breast cancer treatment, as this aggressive subtype lacks hormone-targeted therapies and demonstrates limited response to conventional approaches.

Chimeric antigen receptor (CAR) T-cell therapy, originally developed for oncology, is being adapted to treat chronic non-malignant diseases sustained by pathological cells including viral reservoirs, autoreactive B cells, fibroblasts, and senescent cells. The review examines how CAR-based strategies can be redirected across diverse disease settings through enhanced co-stimulatory domains like CD28 and 4-1BB, PD-1–CD28 switch receptors that reverse inhibitory signaling, and cytokine-resistant CARs incorporating dominant-negative TGF-β receptors. Applications span infections (HIV and EBV), autoimmune conditions (targeting CD19 and BCMA), fibrosis (targeting FAP), hemophilia (using BAR-CARs), transplantation (employing HLA-specific CAR-Tregs), and senescence-related pathologies (targeting uPAR and NKG2DLs). Early clinical data from systemic lupus erythematosus, systemic sclerosis, myositis, and multiple sclerosis alongside preclinical successes demonstrate feasibility and durable disease modification. These developments position programmable cellular immunotherapy as a broadly applicable platform for eliminating persistent pathological cells, remodeling diseased tissue environments, and restoring long-term immune homeostasis beyond cancer treatment.

Relapsed or refractory acute lymphoblastic leukemia (R/R ALL) represents a significant challenge in hematologic oncology, traditionally managed through salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation. Recent immunotherapy advances, including CAR-T cell therapy and bispecific T-cell engagers, have fundamentally transformed treatment approaches, enabling deep remissions in heavily pretreated patients. These innovations extend beyond conventional salvage chemotherapy, offering previously unavailable therapeutic options. However, leukemia cells develop resistance mechanisms under selective pressure from treatment. Following CD19-directed immunotherapy, resistance emerges through multiple pathways including antigen escape via genetic alterations, aberrant splicing, antigen internalization, trogocytosis, and lineage switching. Understanding that R/R ALL represents an evolved disease with altered clonal architecture is clinically crucial, as each treatment modifies subsequent disease characteristics. Blinatumomab, a CD19×CD3 bispecific T-cell engager, activates T-cells without requiring ex vivo cellular engineering, representing a distinct mechanistic approach. These evolving treatment modalities and their implications for sequencing and resistance mechanisms will be central topics at LeukO 2026, a virtual global congress on leukemias scheduled for September 3-4.

Allogeneic CAR-T cell therapy represents a significant advancement in cancer treatment by addressing a critical limitation of traditional personalized immunotherapy: extended manufacturing timelines. Unlike conventional autologous CAR-T approaches, which require collecting cells from individual patients and customizing them in the laboratory—a process that can take weeks—allogeneic CAR-T therapy utilizes healthy donor cells to create ready-to-use treatments available immediately when patients need them. This approach eliminates prolonged waiting periods that can be detrimental for patients with rapidly progressing diseases. Liv Hospital emphasizes that this innovation democratizes access to life-saving cellular immunotherapy across geographic locations and urgent medical situations. The manufacturing process requires precision at every stage, from cell selection through expansion, ensuring both potency and safety while maintaining standardized protocols. By leveraging allogeneic CAR-T technology, healthcare providers can treat more patients faster, fundamentally transforming how cellular immunotherapy is delivered and making advanced cancer treatments more accessible to populations worldwide.

In situ cancer vaccination, also termed intratumoral immunotherapy, represents an innovative approach that transforms tumors into endogenous vaccine platforms by leveraging the tumor itself as an antigen source. Unlike conventional tumor-associated antigen or personalized neoantigen vaccines requiring predefined targets and complex manufacturing, in situ vaccination presents the tumor's complete antigenic repertoire—including tumor-associated antigens, neoantigens, post-translationally modified epitopes, and viral antigens in their native context. This comprehensive antigen exposure elicits robust polyclonal cytotoxic T-cell responses and reduces immune escape driven by tumor heterogeneity. The approach activates multiple immune mechanisms through programmed cell death pathways including immunogenic apoptosis, pyroptosis, necroptosis, and ferroptosis, which release tumor antigens and danger-associated molecular patterns that promote dendritic-cell activation and durable T-cell responses. Recent advances in nanomedicine-enabled delivery systems and combinatorial strategies with immune checkpoint blockade are overcoming clinical translation barriers such as inconsistent immunogenic cell death induction and suboptimal therapeutic retention. These innovations position in situ cancer vaccination as a broadly applicable, patient-tailored immunotherapy capable of generating durable systemic antitumor immunity.

The limitations and developmental directions of polyurethane materials in cardiovascular therapy are reviewed. The mechanisms underlying the poor biostability of polyurethane materials are elucidated, and research progress in corresponding enhancement methods is provided. Modification methods to enhance polyurethane for use in cardiovascular materials are discussed. The macroscopic morphology and processing techniques required for polyurethane materials in cardiovascular applications are discussed.

The phase 2 Neo-CheckRay trial evaluated combining immune-modulating stereotactic body radiation therapy (iSBRT) with neoadjuvant chemotherapy and immunotherapy in high-risk estrogen receptor–positive, HER2-negative early breast cancer. The randomized study of 147 patients compared three treatment arms: chemotherapy plus iSBRT alone, iSBRT plus the anti–PD-L1 antibody durvalumab (Imfinzi), and iSBRT plus durvalumab with the anti-CD73 antibody oleclumab. Results, published in Nature Medicine, demonstrated that durvalumab significantly improved pathologic complete response rates from 16.7 percent to 29.4 percent in the primary analysis, with gains reaching statistical significance in the per-protocol population at 32.6 percent. Notably, the greatest therapeutic benefit occurred in PD-L1–negative tumors. Adding oleclumab did not provide additional advantage over durvalumab monotherapy. These findings suggest that combining iSBRT with anti–PD-L1 immunotherapy offers meaningful clinical benefit for selected early breast cancer patients, potentially improving surgical outcomes and informing future treatment strategies.

Researchers have evaluated a novel phage-inclusive multimodal strategy designed to address recurrent urinary tract infections, a persistent clinical challenge affecting millions globally. This study, published in BMC Microbiology in August 2026, represents an open access contribution to advancing treatment options beyond conventional antibiotic approaches. The multimodal strategy integrates bacteriophage therapy with complementary therapeutic interventions, leveraging the unique antimicrobial properties of phages to target uropathogens resistant to traditional antibiotics. The evaluation likely assessed efficacy, safety, and clinical outcomes in patients experiencing recurrent infections, measuring metrics such as infection recurrence rates and symptom resolution. This research matters significantly as antibiotic resistance continues escalating worldwide, making alternative therapeutic approaches increasingly critical. Phage therapy offers promising potential to circumvent resistance mechanisms while reducing dependence on conventional antibiotics, thereby improving patient outcomes and addressing a major public health concern. The open access publication ensures broad dissemination of findings to the scientific and clinical communities, potentially accelerating adoption of innovative treatment strategies for recurrent urinary tract infections.

Chimeric antigen receptor T-cell (CAR T) therapy has revolutionized blood cancer treatment for over a decade, and researchers are now combining it with gene-editing technologies like CRISPR and TALEN to expand applications into rare diseases. CRISPR Therapeutics is developing next-generation gene-edited CAR T therapies designed as off-the-shelf products rather than custom treatments, using CRISPR-Cas9 to make multiple genetic modifications that create more potent, durable, and scalable cancer treatments while reducing manufacturing complexity. Gene editing enhances CAR T cells with additional capabilities, improving their performance, safety, and durability by addressing current limitations. Experts including Philippe Duchateau at Cellectis and Cesar Sommer at Allogene Therapeutics emphasize that gene editing enables greater precision in cell therapy design, allowing targeted edits that improve T cell function, resistance to exhaustion, and safety profiles. Beyond oncology, recent studies demonstrate CAR T's potential in autoimmune conditions like systemic lupus erythematosus, myasthenia gravis, and stiff-person syndrome by targeting B cells and plasma cells that produce harmful autoantibodies, effectively resetting the immune system while gene editing further enhances cell persistence and safety.

Triple-negative breast cancer (TNBC) remains a challenging malignancy with poor prognosis despite advances in conventional therapies. Recently, neoadjuvant immunotherapy has emerged as a promising strategy to improve clinical outcomes, building upon encouraging results from landmark trials including KEYNOTE-522 and IMpassion031. These studies have validated the efficacy of programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors such as pembrolizumab and atezolizumab as neoadjuvant agents. The therapeutic landscape has expanded beyond PD-1/PD-L1 targeting to encompass additional biomarkers including Forkhead Box Protein P3 (FOXP3) and Wilms' Tumor gene 1 (WT1), enabling more personalized treatment approaches. However, substantial heterogeneity in trial design, participant demographics, and clinical endpoints has created divergent findings across studies. This comprehensive review synthesizes the principal biomarkers driving neoadjuvant immunotherapy in breast cancer, elucidates their underlying mechanisms of action, and consolidates data from ongoing and completed clinical studies. By clarifying the evolving role of biomarker-driven neoadjuvant immunotherapy, this work provides critical guidance for optimizing breast cancer management and improving patient outcomes in this aggressive disease subtype.

Urinary tract infections represent a major global health burden affecting over 400 million people annually, with recurrent infections driving antibiotic resistance and limiting treatment options. This study investigated bacteriophage therapy as an alternative approach to combat uropathogenic Escherichia coli infections that establish persistent intracellular reservoirs within bladder epithelial cells. Using an in vitro bladder infection model, researchers demonstrated that lytic phages can penetrate bladder epithelium through direct cellular uptake or via co-invasion with extracellular bacteria, revealing a previously unknown bacteria-assisted delivery pathway that enhances intracellular phage access. Significantly, the presence of extracellular UPEC substantially increased intracellular phage uptake, potentially facilitating targeting of internalized bacterial reservoirs. Phage treatment effectively prevented epithelial infection and preserved urothelial cell integrity while reducing intracellular bacterial burden, though complete eradication was not achieved and efficacy was limited to early infection stages. These mechanistic findings advance understanding of phage-pathogen-human interactions and provide critical insights for optimizing phage-based therapeutic strategies to address recurrent urinary tract infections and circumvent antimicrobial resistance challenges.

Cell therapy represents a transformative approach to cancer treatment, offering potential one-time interventions capable of delivering durable responses and even cure. Since the first chimeric antigen receptor T-cell (CAR T) therapy gained approval in 2017, these autologous cell therapies—which isolate and genetically modify a patient's own T-cells to target tumors—have dramatically improved outcomes for blood cancers including lymphomas and multiple myelomas, with early promise emerging in solid tumors. However, the personalized manufacturing process remains time-intensive and challenging to scale globally. AstraZeneca is addressing these limitations through multiple strategies: accelerating autologous cell therapy manufacturing while simultaneously advancing next-generation approaches including allogeneic and in vivo cell therapies. The company prioritizes developing more effective treatments for multiple myeloma patients, who currently face significant treatment burdens including frequent hospital visits, intensive monitoring, and relapse risks. These innovative approaches aim to overcome manufacturing and scalability barriers, expanding access to cell therapy for more cancer patients worldwide while reducing the physical and emotional toll of prolonged treatment cycles.

Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 receptors, making hormone and HER2-targeted therapies ineffective. Chemotherapy remains the primary systemic treatment, though immunotherapy and antibody-drug conjugates have recently expanded options. For early-stage TNBC, treatment typically involves surgery, radiation if indicated, and adjuvant chemotherapy. Patients with BRCA mutations may benefit from olaparib (Lynparza) for one year post-chemotherapy, potentially improving survival. Neoadjuvant chemotherapy, sometimes combined with pembrolizumab (Keytruda), can shrink tumors before surgery. For metastatic TNBC, approximately one in five cases are PD-L1 positive. The sacituzumab govitecan (Trodelvy) plus pembrolizumab combination now represents a top first-line treatment option, significantly improving progression-free survival compared to traditional chemotherapy plus pembrolizumab alone. Despite treatment challenges from limited targeted options, early-stage TNBC often responds well to chemotherapy, with many patients achieving favorable outcomes when tumors are eliminated before surgery.

As neurodegenerative disease therapies including gene, cell, and oligonucleotide treatments advance through clinical development, pharmaceutical sponsors face a critical challenge: selecting appropriate preclinical models for evaluating central nervous system delivery. While rodent models remain valuable for early proof-of-concept studies, their anatomical and physiological differences limit predictive accuracy for human translation. Nonhuman primates offer superior translational confidence but face availability constraints and escalating costs. Consequently, the Göttingen minipig is emerging as a scientifically rigorous yet more accessible alternative for CNS therapeutic development. According to Erin Slosarek, preclinical CNS lead at Labcorp, successful CNS delivery requires integrated scientific decisions centered on the blood-brain barrier, which selectively limits therapeutic access to the brain and spinal cord. The minipig model balances translational relevance with practical scalability, offering sponsors a middle ground between rodent simplicity and primate complexity. Key considerations include foundational CNS development factors, species selection criteria, dosing strategies, and routes of administration. For sponsors developing advanced CNS therapies, understanding where each preclinical model fits within the development landscape is essential for optimizing translational success.

Recurrent urinary tract infections represent a significant clinical challenge, particularly for women, with limited treatment success through conventional antibiotics. This study introduces a novel combined therapeutic approach using bacteriophage therapy paired with faecal microbiota transplantation to address infections caused by Escherichia coli. Three female patients with long-standing recurrent UTIs—requiring four to ten antibiotic treatments annually over five to forty-four years—received oral and intravesical phage therapy for eight days using a two-phage cocktail consisting of E. coli phages E2 and phi41S. Two patients subsequently underwent faecal microbiota transplantation. The treatments were well tolerated with minimal adverse effects. Although E. coli remained detectable in follow-up samples, all patients experienced none or significantly fewer and less severe UTI episodes during the twenty-four-month post-treatment period. This represents the first clinical application combining phage therapy with faecal microbiota transplantation for recurrent UTIs, offering a promising alternative to antibiotic-dependent strategies and potentially addressing the broader antimicrobial resistance challenge posed by excessive antibiotic consumption in UTI management.

This 2026 article published in Frontiers in Immunology examines multi-antigen chimeric antigen receptor-T cell (CAR-T) therapy as a treatment approach for relapsed and refractory B cell lymphomas. Authored by Pandey, Samat, Dahiya, and Patel, the work addresses a significant clinical challenge in hematologic malignancies where patients fail to respond to or relapse following standard treatment protocols. The research focuses on tandem CAR technology, which enables simultaneous targeting of multiple antigens on B cell lymphoma cells rather than single-target approaches. This multi-antigen targeting strategy is designed to reduce tumor escape mechanisms that often occur when cancer cells downregulate or lose expression of individual targeted antigens. The article's emphasis on tandem CAR platforms represents an advancement in immunotherapy precision, potentially improving therapeutic efficacy and durability of response in difficult-to-treat lymphoma patients. This work matters because relapsed and refractory B cell lymphomas remain a serious clinical problem with limited treatment options, and multi-antigen CAR-T approaches offer a promising strategy to overcome resistance mechanisms and improve patient outcomes.

Axicabtagene ciloleucel's FDA approval in 2017 marked a watershed moment for CAR-T cell therapy in blood cancer treatment. Now entering its second decade, Dr. Sattva S. Neelapu, principal investigator of the landmark ZUMA-1 trial and a founding architect of CD19 CAR-T technology, provides a comprehensive assessment of the field's progress and trajectory through 2036. Some early predictions proved accurate—CAR-T successfully replaced autologous stem cell transplants in second-line settings and gained approvals for indolent lymphomas. However, other forecasts, including movement to first-line use, third and fourth-generation constructs, allogeneic product approvals, and expansion into T-cell malignancies and solid tumors, have largely remained unfulfilled. Neelapu candidly acknowledges his historically poor timing predictions while maintaining that underlying biology validates the science. His five evidence-based forecasts for the next decade emphasize frontline use in high-risk lymphoma, dual-target CAR technologies, allogeneic products, in vivo delivery systems, and initial T-cell malignancy approvals. A consistent finding across disease contexts demonstrates that earlier treatment lines produce superior outcomes through enhanced T-cell fitness, suggesting this principle will drive future CAR-T applications.

Pour la première fois, un patient a reçu une thérapie génique visant à rajeunir ses cellules. Testée contre le glaucome, cette approche pourrait ouvrir la voie à la régénération d’autres organes que l’œil.

Cardiac pacemakers are critical for treating heart rhythm disorders, but traditional implants are associated with great risks and complications owing to their invasive nature. Here we introduce a wearable non-invasive ultrasound pacemaker (NUP) that activates engineered sonogenetic ion channels (MscL-G22S) to modulate cardiomyocytes, achieving spatiotemporally controlled precise cardiac pacing. In vitro studies on transfected human cardiomyocytes demonstrated synchronized calcium signalling and controlled responses to ultrasound stimulation. In vivo experiments in rats showed non-invasive pacing with high spatial precision (less than 1 mm) and frequency control (up to 9 Hz) stimulations in different heart chambers, restoring sinus rhythm in arrhythmic models. We validated long-term safety during daily activities in rats over 8 months. To assess translational potential, we show the genetic safety of NUP and demonstrated its feasibility for human-scale applications in ex vivo porcine models. With its compact, wearable design and imaging-guided stimulation, the NUP offers a non-invasive, safe and adaptable pacemaker solution for cardiac rhythm management.

Recent research presents the human gut microbiome as a promising new frontier in drug discovery. Author Gonzalo Colmenarejo's comprehensive review, published in Frontiers in Drug Discovery, explores innovative therapeutic approaches that leverage the complex microbiome-host system to develop novel treatments. The study examines multiple intervention strategies including probiotics, prebiotics, postbiotics, and bacteriophages, alongside established techniques like fecal microbiota transplantation. A key focus involves harnessing microbial metabolites—bioactive compounds produced by gut bacteria—as potential therapeutic agents. This paradigm shift recognizes that modulating the microbiome composition and function can influence host health and disease states across multiple physiological systems. The research underscores why this represents a transformative approach: the gut microbiota's role in immune function, metabolism, and neurological health creates unprecedented opportunities for targeted interventions. By understanding these intricate interactions, pharmaceutical development can exploit the microbiome as both a drug target and delivery mechanism, opening entirely new pathways for treating previously intractable conditions.