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Antibody drug conjugates in recurrent or metastatic cervical cancer: a focus on tisotumab vedotin state of art.

Cervical cancer (CC) is still characterized by a poor prognosis despite the progress made in its treatment in recent years. Although immunotherapy has improved outcomes for advanced/recurrent disease, there is a significant gap in addressing patients' needs when they progress after platinum and immunotherapy treatments. In this setting, traditional chemotherapy showed limited effectiveness. In this context, antibody-drug conjugates (ADCs) emerged as a promising tool within targeted cancer therapies. Tisotumab vedotin (TV), an ADC targeting tissue factor, represents the first ADC approved by th

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… Additionally, TV is conjugated with the microtubule-disrupting agent MMAE and a protease-cleavable valine–citrulline linker. …

Oncofetal Chondroitin Sulfate Is a Highly Expressed Therapeutic Target in Non-Small Cell Lung Cancer.

Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC. High oncofetal CS expression is associated with shorter disease-free survival and poor overall survival of clinically annotated stage I and II NSCLC patients (n = 493). Oncofetal CS qualifies as an independ

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… Preparation of Drug Conjugate VDC-MMAE and Control-MMAE We chemically conjugated a potent anti-mitotic agent, monomethyl auristatin E (MMAE), derived from peptides occurring in marine shell-less mollusk Dolabella auricularia to rVAR2 via a maleimide-activated cathepsin B valine-citrulline cleavable …

Fate of Antibody-Drug Conjugates in Cancer Cells.

Antibody-Drug Conjugates (ADCs) are a class of cancer therapeutics that combines antigen specificity and potent cytotoxicity in a single molecule as they are comprised of an engineered antibody linked chemically to a cytotoxic drug. Four ADCs have received approval by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) and can be prescribed for metastatic conditions while around 60 ADCs are currently enrolled in clinical trials. The efficacy of an ADC greatly relies on its intracellular trafficking and processing of its components to trigger tumor cell death. A limite

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… Brentuximab vedotin; SGN-35) is a chimeric monoclonal anti-CD30 antibody cAC10 bound to the auristatin agent MMAE via an enzymatic cleavable valine-citrulline (vc) – paminobenzyl alcohol (PAB) linker, with a DAR of 4:1 [ 45 ]. …

Exploring the Vasculitis-Tumors Link: Epidemiological Patterns, Mechanistic Insights, and Clinical Implications.

This review systematically examines the association between vasculitis and malignancies by summarizing the risk of tumor-associated vasculitis, their clinical characteristics, and proposed pathogenic mechanisms across different vasculitic subtypes. Relevant case reports and mechanistic studies are integrated to provide a comprehensive overview of this entity. The findings offer practical value for rheumatologists in distinguishing primary vasculitis from malignancy-associated forms and optimizing patient surveillance, and for oncologists in improving recognition of tumor-associated vasculitis

Alcohol Consumption and Autoimmune Diseases.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system's regulatory mechanisms to avoid attacking the body's tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immun

Humanized Bone Model Identifies BMP6 as a Multifunctional Regulator in Myeloma Bone Disease.

Multiple myeloma (MM) is a plasma cell malignancy that disrupts bone homeostasis by suppressing osteogenesis and promoting osteoclast activity. While most therapeutic interventions to date have focused on targeting tumor cells and reducing osteolysis, we investigate whether osteoinductive strategies can restore bone formation and counteract disease progression. Using a human bone marrow-like scaffold model that enables direct in vivo evaluation of tumor-stroma interactions and human bone formation, we demonstrate that MM-derived mesenchymal stromal cells (MSCs) retain osteogenic potential but

Exosomes in the Repair of Bone Defects: Next-Generation Therapeutic Tools for the Treatment of Nonunion.

Nonunion with bone defects, a common complication after long bone fracture, is a major challenge for orthopaedic surgeons worldwide because of the high incidence rate and difficulties in achieving successful treatment. Bone defects are the main complications of nonunion. The conventional biological treatments for nonunion with bone defects involve the use of autologous bone grafts or bone graft substitutes and cell-based therapy. Traditional nonunion treatments have always been associated with safety issues and various other complications. Bone grafts have limited autologous cancellous bone an

Antibodies to watch in 2026.

The Antibodies to Watch article series provides annual updates on commercial late-stage clinical development, regulatory review, and marketing approvals of antibody therapeutics. Since the first article was published in 2010, the late-stage pipeline has grown from 26 antibody therapeutics to over 200, while during the same time numerous molecules in late-stage studies either transitioned to regulatory review and were approved or were terminated. In this installment of the series, we recap first marketing approvals granted to 19 antibody therapeutics in 2025, discuss 26 molecules currently in r

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… Trastuzumab botidotin (A166, 舒泰萊®) is an ADC composed of a humanized anti-HER2 IgG1κ antibody conjugated to Levena Biopharma’s proprietary tubulin inhibitor Duo-5 toxin via a stable protease-cleavable valine-citrulline linker and site-specific (DAR 2) K-Lock™ conjugation chemistry. … Becotatug vedotin (MRG003, MEIYOUHENG®) is an ADC developed by Shanghai Miracogen and Lepu Biopharma in which the microtubule-disrupting agent MMAE is conjugated to a humanized anti-EGFR IgG1κ antibody via a cleavable valine-citrulline linker (average DAR = 4). …

Epidemiology, Pathophysiology, and Management of Cancer-Associated Ischemic Stroke.

Cancer and stroke are leading causes of global disability and mortality. With improvements in cancer-associated mortality and advancements in treatment of active malignancy, it is more common to encounter patients with ischemic stroke and active malignancy. Evidence suggests that cancer-associated ischemic stroke is a unique subtype of stroke; however, there is limited guidance when considering diagnostic workup, secondary prevention, rehabilitation, and future directions within this population. In this narrative review, we aim to describe the epidemiology, pathophysiological mechanisms, manag

Systemic lupus erythematosus: pathogenesis and targeted therapy.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress

The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.

Purpose of reviewIn this review, we describe the interaction between B cells and bone during development, aging, and disease. RECENT FINDINGS: There is an increased interest in identifying the mechanisms of interaction between immune cells and the skeletal system. This knowledge is critical for understanding the pathology of autoimmune diseases and developing therapeutic interventions. Humoral immunity depends on B cells and their secreted immunoglobulin (antibodies). Earlier studies described B cell influence on the skeletal system, with a major focus on the role of plasma cells and secreted

The impact of gut microbial signals on hematopoietic stem cells and the bone marrow microenvironment.

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiation in the bone marrow, which is tightly regulated by cues from the microenvironment. The gut microbiota, a dynamic community residing on the mucosal surface of vertebrates, plays a crucial role in maintaining host health. Recent evidence suggests that the gut microbiota influences HSCs differentiation by modulating the bone marrow microenvironment through microbial products. This paper comprehensively analyzes the impact of the gut microbiota on hematopoiesis and its effect on HSCs fate and differentiation by modifying the b

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… Early hematopoietic injury triggered by benzene characterized with inhibition of erythrocyte differentiation involving the mollicutes_RF39-derived citrulline . Chemosphere ( 2022 ) 303 : 135009 . doi: 10.1016/j.chemosphere.2022.135009 35597459 91 Xiao HW Cui M Li Y Dong JL Zhang SQ Zhu CC . …

Effects of Obesity and Calorie Restriction on Cancer Development.

The risk of malignant tumor development is increasing in the world. Obesity is an established risk factor for various malignancies. There are many metabolic alterations associated with obesity which promote cancerogenesis. Excessive body weight leads to increased levels of estrogens, chronic inflammation and hypoxia, which can play an important role in the development of malignancies. It is proved that calorie restriction can improve the state of patients with various diseases. Decreased calorie uptake influences lipid, carbohydrate and protein metabolism, hormone levels and cell processes. Ma

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… The decreased metabolites consisted mainly of amino acids or related metabolites, including ornithine, citrulline and taurine. The level of the pro-aging amino-acid methionine was also depleted. Fasting led to an increase in the beta-hydroxybutyrate levels. …

Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer.

The HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) is approved for the treatment of metastatic, HER2-positive breast cancer after prior trastuzumab and taxane therapy, and has also demonstrated efficacy in the adjuvant setting in incomplete responders to neoadjuvant therapy. Despite its objective activity, intrinsic and acquired resistance to T-DM1 remains a major clinical challenge. T-DM1 mediates its activity in a number of ways, encompassing HER2 signalling blockade, Fc-mediated immune response and payload-mediated microtubule poisoning. Resistance mechanisms relating t

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… Trastuzumab duocarmazine (SYD985) [vic-]trastuzumab duocarmazine (SYD985, Synthon), another HER2-targeting ADC, comprises a valine-citrulline- seco duocarmycin hydroxybenzamide azaindole (vc- seco -DUBA) payload conjugated to trastuzumab by a cleavable linker at a DAR of 2.8. 67 vc- seco -DUBA is a …

Targeting the Post-Irradiation Tumor Microenvironment in Glioblastoma via Inhibition of CXCL12.

Radiotherapy is a mainstay in glioblastoma therapy as it not only directly targets tumor cells but also depletes the tumor microvasculature. The resulting intra-tumoral hypoxia initiates a chain of events that ultimately leads to re-vascularization, immunosuppression and, ultimately, tumor-regrowth. The key component of this cascade is overexpression of the CXC-motive chemokine ligand 12 (CXCL12), formerly known as stromal-cell derived factor 1 (SDF-1). We here review the role of CXCL12 in recruitment of pro-vasculogenic and immunosuppressive cells and give an overview on future and current dr

Computational Drug Repurposing Across the Multiple Myeloma Spectrum: From MGUS to MM.

Background/objectivesMultiple myeloma (MM) is a challenging, B cell malignancy characterised by the uncontrolled proliferation of plasma cells within the bone marrow. Despite significant advances in treatment options nowadays, MM remains an incurable malignancy, with the majority of patients succumbing to the disease. MM develops from a pre-malignant state known as monoclonal gammopathy of unknown significance (MGUS), which then has the potential to evolve either into smouldering (asymptomatic) multiple myeloma (SMM) or into MM. Since novel drug discovery takes years to reach the clinic, drug

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

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… No correction further occurred for decreased citrulline in frontal cortex. On the other hand, the increased ratio PI 18:0_20:4 / total PIs was normalized and the decreased ratio of odd-chain to even-chain fatty acid SMs was partially normalized ( Figure 3A ). …

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas.

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. Th

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… Brentuximab vedotin (BV) is an anti-CD30 humanized IgG monoclonal antibody combined with the antimitotic agent monomethylauristatin E (MMAE) via a cathepsin cleavable linker (valine-citrulline). The randomized phase III ALCANZA trial approved BV for the treatment of CTCL [ 15 ]. …

Влияние жизненных поступков, способствующих укреплению здоровья, на микробиоту у выживших жертв гематологического рака: обзор скопирования.

Целью этого аналитического обзора является изучение взаимосвязи между поведением, способствующим здоровому образу жизни, и микробиотой кишечника у выживших жертв гематологического рака, включая лейкемию, лимфому и множественную миелому. С учетом растущего числа таких случаев и связанных с этим проблем с лечением понимание того, как факторы образа жизни влияют на состояние здоровья, может дать представление о том, как улучшиться состояние выживших жертв. МЕТОДЫ: Мы провели всеобъемлющий поиск по нескольким базам данных, включая PubMed/Medline, CINAHL и Scopus, вслед за предпочтительными элемент

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… Studies have shown that a healthy nutritional status and a well‐maintained gut barrier are protective factors against GvHD, and poor nutritional status and reduced plasma citrulline levels, the most sensitive indicator of intestinal barrier health, predict the likelihood of developing acute GvHD following …

Mass Spectrometry-Based Proteomics: Analyses Related to Drug-Resistance and Disease Biomarkers.

Mass spectrometry-based proteomics is a key player in research efforts to characterize aberrant epigenetic alterations, including histone post-translational modifications and DNA methylation. Data generated by this approach complements and enrich datasets generated by genomic, epigenetic and transcriptomics approaches. These combined datasets can provide much-needed information on various mechanisms responsible for drug resistance, the discovery and validation of potential biomarkers for different diseases, the identification of signaling pathways, and genes and enzymes to be targeted by futur