Search Results (5,231)

Mesothelin (MSLN) is a cell surface glycoprotein with limited expression in normal tissues but frequent overexpression in solid tumors, including gynecological malignancies. This review summarizes the state of the art on the biological role, diagnostic value, prognostic significance, and therapeutic potential of MSLN in ovarian, endometrial, and cervical cancers. Evidence from clinical and experimental studies indicates that MSLN contributes to tumor progression through interactions with CA125, promotion of cell adhesion and peritoneal metastasis, activation of oncogenic signaling pathways, modulation of immune responses, and development of chemoresistance. Elevated MSLN expression has been associated with advanced clinical stage of the disease, platinum resistance, and poorer survival outcomes, particularly in ovarian cancer patients, although prognostic findings remain inconsistent. Circulating soluble MSLN may serve as a minimally invasive biomarker and may improve diagnostic accuracy when combined with established markers. Therapeutic MSLN strategies—antibody-drug conjugates, CAR-T and NK cell therapies, monoclonal antibodies, immunotoxins, vaccines, and checkpoint blockade—provide promising pre-clinical and early clinical results, particularly in resistant or recurrent forms of the disease. Overall, MSLN constitutes a promising target for precision oncology in gynecological cancers, although further clinical studies are required to validate its diagnostic utility and optimize targeted therapeutic approaches. Full article

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy and the second leading cause of cancer-related mortality worldwide, underscoring the need for the development of more effective and durable therapeutic strategies. A key mechanism of tumor immune evasion involves activation of immune checkpoint pathways through the upregulation of inhibitory ligand expression within the tumor microenvironment, leading to lymphocyte exhaustion and impaired antitumor immunity. Consequently, immune checkpoints have emerged as important targets for immunotherapeutic intervention, with significant advances over the past decade. Nevertheless, despite demonstrated clinical benefits in selected patient subpopulations, the overall therapeutic efficacy of immune checkpoint inhibitors remains limited, particularly in the context of CRC. In this review, we provide a comprehensive overview of currently approved immune checkpoint-based immunotherapies for cancer treatment, with a specific focus on CRC, as well as ongoing clinical trials and evolving trends in this area. Furthermore, we discuss emerging targets and novel therapeutic strategies, with particular emphasis on innovative small-molecule inhibitors as potential alternatives to monoclonal antibody-based approaches. Finally, we outline future perspectives and potential directions for advancing immune checkpoint-targeted therapies in CRC. Full article

Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer’s disease (AD), especially during anti-amyloid-β (Aβ) monoclonal antibody (Aβ-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate TSPO-associated neuroinflammatory responses to chronic Aβ-mAb therapy and their modulation by the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone. App^NL-G-F knock-in mice underwent TSPO-PET and Aβ-PET imaging at 5, 7.5, and 10 months of age across four treatment arms: placebo, Aβ-mAb, pioglitazone, and combination therapy. TSPO-PET detected early and progressive neuroinflammatory responses to Aβ-mAb that appeared lower with pioglitazone co-treatment. Both mono- and combination therapy were associated with altered temporal and spatial dynamics of the TSPO-PET signal. In addition, we applied a previously validated microglia desynchronization index based on TSPO-PET connectivity, which captured individual variation in regional TSPO-PET organization and correlated with cognitive performance. Together, TSPO-PET and its regional synchronicity can quantify longitudinal, region-specific treatment effects, which may help differentiate harmful from adaptive neuroinflammatory responses. These findings highlight the potential of TSPO-PET as a stratification biomarker to optimize therapeutic interventions. TSPO-PET therefore enables in vivo tracking of treatment-associated neuroinflammatory responses during anti-Aβ immunotherapy and provides a non-invasive framework for evaluating combination strategies targeting amyloid pathology and immune regulation in AD. Full article

Purpose: Lymph node (LN) excision is critical in oncologic surgery to provide important therapeutic and diagnostic information. LN evaluation helps in staging cancers, predicting prognosis and improving survival. The ultimate wish of a surgical oncologist would be to localize and dissect all pathologically positive LNs while avoiding the morbidity of removing true negative LNs. The goal of our study was to identify a reliable marker for clinical prediction of LNs with cancer cells from non-small cell lung cancer (NSCLC) versus LNs without. We identified epithelial cell adhesion molecule (EpCAM), a membrane protein normally expressed in epithelial tissues, including in lung. Patients and Methods: We used human specimens immunostained with anti-EpCAM monoclonal antibody. Results: EpCAM was expressed in NSCLC metastasis to LNs, as shown in 74 positive LNs from patients with resected primary NSCLC. Among pathologically negative LNs, regardless of PET avidity, EpCAM was absent; whereas among pathologically positive LNs, all PET uptake groups exhibited high EpCAM positivity. Together, these biomarkers had a 100% accuracy. There was no difference in expression between hilar and mediastinal LNs, nor between primary tumor histology. Conclusions: EpCAM may be useful for the surgical oncologist for preoperative or intraoperative detection of positive LNs from NSCLC. Full article

Background/Objectives: Vaccine development pipelines are forward-looking indicators of public health preparedness, reflecting the capacity to address unmet medical needs and emerging threats. This descriptive analysis aims to characterise the 2025 clinical-stage pipeline of infectious disease vaccines and prophylactic monoclonal antibody candidates developed by Vaccines Europe member companies, and to describe how pipeline characteristics address evolving public health priorities. Methods: A descriptive analysis was conducted using publicly available data compiled in the Vaccines Europe Pipeline Review 2025, with validation by participating companies. Candidates in clinical development or regulatory review were classified using a standardised framework by pathogen/disease, target population, public health priority, and technologies. Results: The Vaccines Europe member company pipeline comprises 91 candidates across clinical development phases, 19% of which are in Phase III and 7% undergoing regulatory review. This pipeline is predominantly targeting respiratory pathogens (75%), with a strong life-course focus (85% evaluated in adults and/or older adults), and sustained activity in bacterial pathogens relevant to antimicrobial resistance. Notably, 41% of candidates were classified as addressing diseases, disease combinations, or indications for which no licenced preventive product exists. This category includes candidates targeting diseases without a preventive solution, as well as novel combination vaccines and therapeutic approaches in areas where individual components or preventive vaccines are already available. This captures vaccines candidates in different stages of development, not necessarily first-in-disease innovation. The pipeline shows broad technological diversity (12 technologies), dominated by RNA approaches and multivalent candidates, with growing focus on climate-sensitive, zoonotic, and pandemic-prone pathogens. Conclusions: Within the pipeline of Vaccines Europe member companies, this analysis describes development activity oriented toward broader prevention, platform-based approaches, and preparedness-relevant targets. As a structured and recurring annual assessment, the Vaccines Europe Pipeline Review supports horizon scanning and evidence-based dialogue between industry and vaccine ecosystem stakeholders. In order to maximise the impact of vaccine development pipelines to public health, predictable investment, streamlined trial and regulatory pathways, strong surveillance, and real-world data systems, coordinated decision-making is required to enable timely and equitable access, and complementary incentive and procurement reforms. Full article

Upper tract urothelial carcinoma (UTUC) accounts for approximately 5–10% of diagnosed urothelial carcinoma (UC). Due to advanced initial presentation or aggressive progression of UTUC, the majority of patients will need systematic treatment in the neo-adjuvant or adjuvant setting. The management of patients with UTUC is complicated due to the lack of published data and only limited studies addressing immunotherapy in UTUC patients are available. The perioperative scenario in localized high-risk disease is still evolving. For metastatic disease, two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab and durvalumab) have obtained approval for the second-line treatment of platinum-pretreated patients. Atezolizumab and pembrolizumab are currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumors. The aim of this review was to highlight the role of immunotherapy in locally advanced and metastatic UTUC and provide the safety profile of these regimens. Full article

Background/objectives: This study presents a mechanistic assessment of an anti-HSPG2 monoclonal antibody (AM6) as an antibody–drug conjugate (ADC) carrier in vitro. Methods: Using live-cell confocal imaging with pathway inhibitors, we qualitatively characterized AM6 internalization and trafficking and compared linker/payload configurations for intracellular delivery and in vitro cytotoxicity. Results: AM6 exhibited rapid cellular entry in MDA-MB-231-LM2 cells, with contributions from clathrin-mediated endocytosis and macropinocytosis, followed by accumulation in endo-lysosomal compartments. Consistent with these trafficking observations, AM6 ADCs bearing cleavable linkers and a potent payload (MMAE) produced more pronounced antiproliferative effects in MDA-MB-231-LM2 and other HSPG2-positive tumor cells than non-cleavable constructs, whereas doxorubicin-based ADCs showed limited activity and greater aggregation risk. Conclusions: Overall, the data inform linker/payload selection and highlight considerations for future work, including quantitative internalization, antigen-negative or knockdown controls, and in vivo pharmacology. Full article

Tauopathies, including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration with tau pathology, are unified by pathogenic tau misfolding, post-translational modification, aggregation, and network-level spread. Yet decades of drug development that predominantly pursued single nodes (e.g., one kinase, one aggregation inhibitor, one monoclonal antibody epitope) have repeatedly delivered late-stage disappointments, underscoring a central lesson: tauopathy behaves less like a linear pathway and more like a coupled system of proteostasis failure, neuroinflammation, synaptic-mitochondrial stress, and metabolic dysregulation. This review examines rhizomes (notably Zingiberaceae genera such as Curcuma, Zingiber, Alpinia, Kaempferia, and Boesenbergia) as chemically diverse “multi-target platforms” whose bioactives can engage several tau-relevant nodes simultaneously. We synthesise evidence across tau phosphorylation (GSK-3β/CDK5 and upstream stress signalling), tau aggregation and seeding, autophagy-lysosome and proteasome pathways, redox-mitochondrial resilience, neuroinflammatory circuits (NF-κB/NLRP3), and neuro-metabolic signalling (insulin-PI3K-AKT, AMPK-mTOR). A translational lens is applied throughout, focusing on drug-likeness and CNS multiparameter optimisation; BBB permeability and efflux; metabolism and bioavailability constraints; and formulation strategies (nanoparticles, phytosomes, engineered exosomes) that may render rhizome-derived scaffolds more clinically plausible. We conclude that rhizomes offer credible mechanistic hypotheses for tau modulation, but progress depends on rigorous standardisation, realistic exposure matching, biomarker-driven study design, and a shift from “single-compound optimism” to network pharmacology with translational discipline. Full article

Objectives: Real-world information on relapsed and/or refractory multiple myeloma (rrMM) clinical management in Portugal is scarce. The CharisMMa Portugal study aimed to characterize rrMM patients through socio-demographic and clinical parameters and describe treatment patterns. Methods: This was an observational, cross-sectional, multicenter study with 62 rrMM patients routinely treated at seven hospitals in Portugal. Data were collected from medical records during clinical appointments (2020–2022) after written informed consent was obtained (ClincialTrials.gov ID-NCT04135963). Patients who were diagnosed with a symptomatic MM episode in the 6 months prior to study initiation and who received treatment before their last relapse episode were enrolled. Results: Most patients were male (54.8%) and living with relatives (90.3%), and almost 50% were independent. Roughly 70% of patients were classified as Revised MM International Staging System (R-ISS) Stage II at diagnosis, with a mean age of 65.76 (±9.24) years old. Most common SliM-CRAB (SLIM: sixty percent or more clonal plasma cells in the bone marrow (S), light chain ratio ≥100 (Li), and MRI-detected focal lesions (M); CRAB: hypercalcemia (C), renal insufficiency (R), anemia (A), and bone lesions (B)) signs were bone lesions (59%), and 62.9% of the patients had at least one comorbidity. At study initiation, 70.5% of patients were on second-line treatment, with monoclonal antibodies and proteasome inhibitors (PIs) + immunomodulators (IMiDs) as leading agents. Triplet regimens were the most common across all lines, while oral and oral + subcutaneous were the most prevalent routes of administration. Conclusions: Triple treatment combinations are common in rrMM management, with PIs and IMiDs frequently used, especially in first-line settings. The use of oral formulation is substantial, suggesting a step toward more patient-centric options. This characterization underscores the complexity of rrMM management and should inform stakeholders of strategies to standardize patient care across reference centers in Portugal. Full article

The pharmaceutical industry has seen significant growth in the development of antibody-based therapeutics, especially monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), used in the treatment of cancer and neurodegenerative diseases. However, their production and purification remain challenging. It is difficult to achieve both high product yield and the strict purity required for clinical use. Downstream processing is expensive and often involves trade-offs between efficiency and product quality. In addition, current purification methods do not fully remove contaminants, especially host cell proteins, residual DNA, and protein aggregates, affecting the safety and effectiveness of the final product. Recent advances in purification technologies, such as improved chromatography techniques and alternative separation methods, have shown promise in addressing some of these limitations. Process optimization and the integration of continuous manufacturing approaches are being explored to enhance efficiency and scalability. Furthermore, increased regulatory expectations are driving the need for more robust and reproducible purification strategies. As the antibody therapeutics market continues to expand, optimizing manufacturing and purification processes is crucial to achieve cost efficiency and large-scale production. This article discusses the main challenges in antibody production and downstream purification, focusing on monoclonal and bispecific antibodies, and compares current strategies to increase yield, improve purity, and reduce contaminants. Full article

Bringing a new drug to market is a complex, costly, and lengthy process, averaging $2.6 billion and about ten years of research and development. It involves multiple stages, from target discovery to post-approval monitoring, and relies heavily on innovation driven by collaboration among pharmaceutical sciences, biology, biochemistry, engineering, and artificial intelligence. Drug discovery can be divided into four main stages: target selection and validation; compound screening and optimization; preclinical studies; and clinical trials. First, researchers identify and validate a biological target associated with a disease using genomic, proteomic, and bioinformatic approaches. Next, potential compounds (“hits”) are identified through methods such as high-throughput and virtual screening, followed by iterative chemical optimization and functional testing. Promising candidates undergo preclinical in vivo studies to assess pharmacokinetics, pharmacodynamics, and toxicity. Clinical development proceeds in three phases: Phase I evaluates safety in healthy volunteers; Phase II assesses efficacy in patients; and Phase III confirms efficacy and safety in larger populations. After successful trials, regulatory agencies review the data for approval. While small molecules have long dominated due to their stability and oral bioavailability, biologics—such as monoclonal antibodies and mRNA-based therapies—have grown rapidly, highlighted by COVID-19 vaccine development and increasing FDA approvals. Full article

Saposin-like protein 2 (SAP2) exhibits strong immunogenicity as an antigen for immunodiagnosis in ruminant and human fasciolosis. Most available immunodiagnostic test kits are based on polyclonal and monoclonal antibodies against antigens from Fasciola spp. Previous studies demonstrated that polyclonal and monoclonal antibodies against SAP2 showed high specificity and could effectively detect Fasciola spp. infections at an early stage. However, polyclonal antibodies are extremely difficult to produce, and quality control is not possible during production; the procedure also involves considerable financial investment. To overcome these problems, we developed a single-chain variable fragment (scFv) to control quality in each production cycle and reduce the cost of manufacturing immunodiagnostic kits. Our objectives were to produce and characterize an scFv that binds the SAP2 from the liver fluke Fasciola gigantica. We constructed the scFv by genetic engineering: we cloned immunoglobulin genes and linked them with flexible polypeptide linkers composed of repeating glycine and serine residues. We selected an scFv with high affinity for binding SAP2 using the phage-display technique and produced it using a prokaryotic expression system. The scFv was characterized via in silico and in vitro methods to confirm its specificity for SAP2, including IMGT/V-QUEST, IMGT/Collier-de-Perles, HADDOCK 2.4, ELISA, immunoblotting, and immunohistochemistry. The scFv was successfully produced and purified using Ni-NTA affinity chromatography. The purified scFvFgSAP2 was approximately 27 kDa, as confirmed by SDS-PAGE and immunoblot analysis. An indirect ELISA and immunoblotting indicated that scFvFgSAP2 had strong reactivity with F. gigantica compared to other parasite species. Moreover, immunolocalization of scFvFgSAP2 confirmed that it binds specifically to natural SAP2 in the cecal epithelium cells of F. gigantica. Therefore, this scFv targeting SAP2 is an effective material and can be used to develop immunodiagnostic procedures. Full article

Cancer stem cells (CSCs) are a distinct subpopulation within a tumor that play an important role in tumor initiation, metastasis, therapeutic resistance, and cancer relapse. Their persistence is strongly influenced by the tumor microenvironment (TME), which provides a range of biological signals that maintain stemness, promote immune evasion, and resistance to cancer treatment. Therefore, effective targeting of CSCs is essential to improve therapeutic efficacy. In this review, we summarize the key characteristics of CSCs and their niche within the TME, emphasizing their interactions with immune cells, stromal components, and secreted factors. We also discuss the major challenges in targeting CSCs, including immune evasion, metabolic constraints, and intratumoral heterogeneity. We further highlight current and emerging immunotherapeutic strategies targeting CSCs, including immune checkpoint inhibitors, cancer vaccines, monoclonal antibodies, nanobodies, bispecific antibodies, antibody-drug conjugates (ADCs), CAR-T and CAR-NK cell therapies, oncolytic viruses, as well as innovative approaches such as targeted protein degradation. Finally, we emphasize the importance of a combinatorial approach that integrates CSCs targeting with modulation of the TME. Together, these strategies may lead to more durable responses, enhance therapy efficacy and reduce the risk of tumor recurrence. Full article

Bongkrekic acid (BKA) is a potent respiratory toxin produced by Pseudomonas cocovenenans. This toxin is commonly found in spoiled fermented rice- and wheat-based products, snow fungus, and black fungus and can cause severe foodborne illness. The development of a rapid onsite detection method can effectively prevent food poisoning incidents and ensure food safety. In this study, a highly specific anti-BKA monoclonal antibody was prepared, the reaction conditions were optimized, and an indirect competitive chemiluminescent enzyme-linked immunoassay (ic-CLEIA) system was developed for high-throughput screening of BKA in food. The results showed that the ic-CLEIA had good linearity in the range of 7.3–106.6 pg/mL, a limit of detection of 4.7 pg/mL, a limit of quantification of 7.3 pg/mL, a half-maximal inhibition concentration of 28.2 pg/mL, a spike recovery of 86.6–94.1%, a coefficient of variation of less than 10%, and no cross-reactivity with structural analogs. There was no significant difference between the detection results obtained with ic-CLEIA and ultraperformance liquid chromatography–tandem mass spectrometry for the samples. This method provides reliable technical support for food safety monitoring, especially for grassroots laboratories and large-scale sample screening. Full article

Nipah virus (NiV) is an animal-borne RNA virus of the genus Henipavirus that poses a significant global health threat. This threat is driven by the virus’s high mortality rate, its capacity to cause epidemics, and the lack of licensed therapeutic interventions or vaccines. Since its initial identification during the 1998–1999 outbreak in Malaysia and Singapore, recurrent episodes have occurred primarily in Bangladesh and India, with mortality rates frequently exceeding 70%. Fruit bats of the genus Pteropus serve as the biological host for the virus. Transmission to humans occurs via contact with infected wildlife, consumption of contaminated products, such as freshly harvested date palm sap, or direct person-to-person exposure. Other modes of transmission, such as transplacentally or via breast milk, are still under investigation. The clinical presentation of NiV infection varies widely, from mild flu-like symptoms to life-threatening respiratory disease and acute encephalitis. It frequently attacks the nervous system, which can lead to coma, permanent neurological damage, or relapsing encephalitis. The virus enters host cells via ephrin-B2/B3 receptors, enabling systemic dissemination and infiltration of the central nervous system. Diagnosis relies primarily on RT-PCR and serological assays, and virus isolation requires high-containment laboratories. Management remains largely supportive, as no approved antiviral therapy exists. Experimental agents, such as remdesivir, favipiravir, and monoclonal antibodies such as m102.4, have shown promise in preclinical studies. Multiple vaccine platforms—including subunit, viral vector, mRNA, and nanoparticle-based approaches—are under development, though none is yet licensed for human use. Strengthened surveillance, infection control measures, and continued research are essential to mitigate the threat posed by this emerging pathogen. This review summarizes current knowledge on NiV, including its virology, epidemiology, pathogenesis, transmission, and recent progress in therapeutic and vaccine development. Full article