Expert Opinion on Biological Therapy最新文献

Introduction: Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequent comorbidities driven by common Type 2 inflammatory pathways. While biologics target both conditions, a standardized definition for 'dual clinical remission' is lacking. This review evaluates the comparative efficacy of current biologics to propose a unified treatment strategy.

Areas covered: We reviewed pivotal phase 3 and 4 trials (including SINUS-52, SYNAPSE, OSTRO, WAYPOINT, and the head-to-head EVEREST trial) evaluating dupilumab, mepolizumab, benralizumab, omalizumab, and tezepelumab. We analyzed outcomes regarding asthma control, nasal polyp reduction, and olfactory recovery. A new composite definition for dual remission - combining zero exacerbations/oral corticosteroids use with clinically meaningful sinonasal improvement - is proposed.

Expert opinion: Achieving dual remission requires a biomarker-guided hierarchy. Dupilumab demonstrates superior efficacy in the 'sinonasal-dominant' phenotype, particularly for olfactory restoration, while anti-IL-5 agents are preferable for the 'exacerbation-dominant' eosinophilic phenotype. Emerging data from the WAYPOINT trial suggests tezepelumab (anti-TSLP) as a potent option for broad epithelial blockade. We advocate moving beyond isolated disease control toward a stratified 'United Airway' remission target guided by fractional exhaled nitric oxide, blood eosinophils, and immunoglobulin E levels.

Introduction: Giant cell arteritis (GCA) is the most common systemic vasculitis in individuals over 50 years of age. Aortic involvement is frequent, often clinically silent, and significantly increases the risk of thoracic aortic aneurysm, underscoring the need for early detection and optimal management.

Areas covered: This review summarizes current knowledge on the pathophysiology, diagnosis, and management of GCA-related aortitis, with emphasis on Th17- and Th1-driven immune pathways and their therapeutic implications. A structured literature search was conducted in major medical databases, including PubMed/MEDLINE, focusing on studies addressing aortic involvement in GCA, imaging modalities for disease assessment, and therapeutic strategies such as glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs, biologic agents, and Janus kinase inhibitors.

Expert opinion: Management should follow a treat-to-target strategy aimed at achieving clinical and, when feasible, imaging remission. Although glucocorticoids remain the cornerstone of treatment, steroid-sparing approaches, particularly with tocilizumab, and emerging targeted biotherapies may improve long-term vascular outcomes and prognosis in selected patients.

Objectives: HER2-positive breast cancer is an aggressive subtype. High-cost originator trastuzumab limits treatment access, making biosimilars like HLX02 a valuable alternative.

Methods: This retrospective real-world study compared HLX02 (n = 42) with originator trastuzumab (n = 237) within the neoadjuvant THP-EC regimen for early HER2-positive breast cancer. The primary endpoint was total pathological complete response (tpCR).

Results: Before propensity score matching (PSM), the tpCR rate was higher with HLX02 (73.81% vs. 43.04%, p < 0.001). After PSM, tpCR rates were comparable (HLX02: 73.81% vs. originator: 72.27%; p = 0.448), with no significant subgroup differences. Safety profiles, including cardiac toxicity, were similar between groups.

Conclusion: HLX02 demonstrated equivalent efficacy and safety to the originator trastuzumab in this setting, representing a cost-effective treatment alternative.

Introduction: Pancreatic cancer is highly aggressive with poor prognosis and limited therapies. Extracellular RNAs (exRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), play key roles in its progression. Transported through vesicles or freely circulating, they regulate proliferation, epithelial-mesenchymal transition, angiogenesis, immune evasion, and metastasis. exRNAs contribute to chemoresistance, immune suppression, tumor growth, and intercellular communication, shaping pancreatic cancer's aggressive phenotype and overall tumor microenvironment.

Areas covered: Recent research highlights exRNAs as prognostic biomarkers and therapeutic targets. Modulating exRNA expression or inhibiting their function may offer new strategies to overcome resistance to existing therapies. This review summarizes current knowledge on the relevance of exRNAs and their potential applications in understanding pathogenesis and improving treatment. A deeper insight into exRNA-mediated signaling networks may help develop innovative therapeutic approaches for more effective pancreatic cancer management in the future.

Expert opinion: Pancreatic cancer, especially pancreatic ductal adenocarcinoma, has poor prognosis due to late diagnosis, aggressiveness, and treatment resistance. exRNAs, including circRNAs, miRNAs, and lncRNAs, regulate tumor progression and are promising biomarkers and therapeutic targets. Despite challenges with stability, delivery, and patient variability, exRNAs show considerable potential for early detection, personalized therapy, genome-editing strategies, and combination treatments with chemotherapy or immunotherapy.

Introduction: Chronic graft-versus-host disease (cGVHD), a frequent, debilitating autoimmune-like syndrome affecting allogeneic transplant recipients begins with inflammatory response to per-transplant tissue injury which evolves into chronic inflammation, T- and B cell dysregulation, and aberrant tissue repair and fibrotic reaction. Monocytes and macrophages contribute to multiorgan inflammation and fibrosis that are hallmarks of cGVHD.

Areas covered: Axatilimab is a high-affinity anti-CSF-1 R humanized immunoglobulin G4 monoclonal antibody that blocks ligand binding to CSF-1 R and downregulates development and differentiation of pathogenic monocyte-derived macrophages. A phase 1/2 study, and subsequently a phase 2 randomized trial that evaluated axatilimab in patient with refractory cGVHD, reported an ORR of 50-74%. Toxicity was dose-dependent. Based on the Phase 2 results, the lowest dosage, 0.3 mg/kg every 2 weeks, was identified as appropriate for the indication. Here, we examine clinical development of axatilimab leading up to its approval by the Food and Drug Administration for treatment of cGVHD after failure of at least two prior therapies.

Expert opinion: Axatilimab has demonstrated safety, tolerability and efficacy in clinical trials; however, many questions remain unanswered including long-term safety data, efficacy when compared to other cGVHD therapies, risks and benefits of axatilimab in combination, and role in earlier lines of cGVHD treatment.

Introduction: Prademagene zamikeracel is an autologous, genetically corrected epidermal graft therapy designed to address the underlying molecular defect in recessive dystrophic epidermolysis bullosa (RDEB). The product is manufactured from a patient's own keratinocytes, which are modified ex vivo to overexpress a normal copy of COL7A1, the gene coding for type VII collagen (C7), which is essential for anchoring fibril formation and stable dermal-epidermal cohesion. In individuals with biallelic COL7A1 variants, loss of C7 results in severe skin fragility, painful and widespread wounds, debilitating scarring, and a high risk of aggressive cutaneous squamous cell carcinoma.

Areas covered: This review outlines the key scientific foundations, translational advances, and clinical trial outcomes that supported regulatory approval of prademagene zamikeracel for use in adult and pediatric patients with RDEB.

Expert opinion: The development of prademagene zamikeracel represents a significant advance in regenerative therapy for RDEB, demonstrating that durable restoration of C7 expression and long-term wound improvement can be achieved through skin grafting.

Introduction: Monoclonal antibodies (mAbs) and antibody - drug conjugates (ADCs) are among the backbones of treatment for relapsed/refractory multiple myeloma (RRMM). Beyond current standard-of-care regimens, the roles of mAbs/ADCs are evolving associated with advances in first-line therapy, emerging data on additional regimens, and developments with immunotherapies and other novel agents.

Areas covered: We review mechanisms of action, efficacy, real-world effectiveness, and key aspects of the safety profiles of daratumumab, isatuximab, elotuzumab, and belantamab mafodotin in RRMM. We consider efficacy in patient subgroups and the challenges of treatment sequencing and highlight new antigen targets and mAb/ADC therapies under investigation. We searched the published literature with PubMed and congress abstracts using drug names or classes and 'myeloma.'

Expert opinion: The widespread use of daratumumab and isatuximab in first-line therapy and evolving roles of CAR T-cell therapies and bispecific antibodies are reshaping RRMM treatment. mAb/ADC-based regimens remain key options in this setting, offering practical, effective, and tolerable approaches for real-world practice. Ongoing research will inform individualized treatment choices and rational sequencing of therapies, with a need for immune-based biomarkers and biologic profiling to enable optimal, integrated use of mAbs, ADCs, CAR T-cell therapies, and bispecific antibodies to further improve outcomes for patients with RRMM.

Introduction: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely arising in the setting of chronic liver disease and cirrhosis. Given the immunosuppressive hepatic tumor microenvironment, optimizing immunotherapeutic strategies is critical to improve patient outcomes.

Areas covered: This review examines the biological rationale and clinical evidence supporting dual immune checkpoint inhibition with nivolumab plus ipilimumab in advanced HCC. We discuss mechanisms of immune tolerance in cirrhosis and tumor progression, including regulatory T cells, myeloid-derived suppressor cells, hypoxia, metabolic reprogramming, and T-cell exhaustion. Key clinical data from early-phase studies, such as CheckMate 040 and the phase III CheckMate 9DW, are analyzed, focusing on overall survival, response rates, and durability of response compared with tyrosine kinase inhibitors. A structured literature search of PubMed, Embase, and major oncology congress proceedings was conducted to identify relevant preclinical and clinical studies.

Expert opinion: Dual checkpoint blockade represents an effective first-line option for selected patients with advanced HCC, offering meaningful survival benefit at the cost of increased immune-related toxicity. Future progress depends on improved patient selection, biomarker development, and rational combination strategies.