Expert Opinion on Biological Therapy最新文献

Introduction: Oncolytic virus (OV) therapy represents a promising approach currently undergoing (pre)-clinical testing for several cancers. Until recently, it was thought that the tropism of oncolytic viruses was restricted to epithelial cancer cells unless they were modified to target additional cell types. It has now become evident that some OVs possess a natural ability to target cancer-associated fibroblasts (CAFs). CAFs are strongly highlighted in supporting cancer progression and impeding anti-cancer therapeutics. Therefore, targeting CAFs in addition to tumor cells could enhance therapy efficacy.

Areas covered: To date, the molecular determinants of tumor cell permissiveness to OV therapy have been thoroughly investigated. The recent notion that CAFs could also be a target for OVs highlights the importance of a comparable understanding of what makes CAFs permissive to OVs. This review explores the various molecular pathways and molecules that may affect the susceptibility of CAFs to OV infection and lysis. We discuss the potential impact of virus entry receptors, microRNAs, Ras and PI3K/AKT signaling, p53 status and type I interferon signaling.

Expert opinion: Further scrutinizing the factors that influence sensitivity of CAFs to OVs can help to identify targets for therapy optimization, especially in tumors with a high abundance of CAFs.

Introduction: Chimeric antigen receptor (CAR) T-cell therapies have rapidly become an integral part of the treatment landscape for relapsed or refractory lymphomas. While early clinical trials demonstrated impressive response rates in patients with multiply relapsed disease and improved outcomes in those with disease refractory to first-line treatments, subsequent longer follow-up has revealed the occurrence of both early and late relapses, as well as the emergence of delayed toxicities.

Areas covered: Ten years after the initiation of the pivotal phase I/II trials that led to the approval of CD19-directed CAR T-cell therapies for large B-cell lymphoma (LBCL), extended follow-up data is now available. This review focuses on the long-term outcomes and toxicities of these therapies, as well as challenges to durable responses and future directions.

Expert opinion: Long-term follow-up has confirmed the curative potential of CAR T-cell therapy in relapsed or refractory LBCL. Toxicities are generally manageable, and although infections remain an important cause of non-relapse mortality, standardized prophylactic approaches can mitigate risk. Advances in CAR T-cell engineering and administration are likely to enhance treatment effectiveness, expand indications, and improve patient outcomes.

Introduction: Antibody-mediated rejection (AMR) is a major obstacle after heart transplantation. Although its pathophysiology is now clearer than a decade ago, clinical management is still fragmented and poorly evidence-based.

Areas covered: Recent work reframes the classic paradigm of donor-specific antibodies (DSA) dependent complement activation as only one axis of injury. Converging data place natural killer (NK) cells at the center of vascular damage: they execute DSA-driven antibody-dependent cellular cytotoxicity (ADCC) via Fcγ receptors and, through 'missing-self' recognition, trigger DSA-negative endothelial injury. These insights have seeded new therapeutic strategies, yet clinical data remain sparse and heterogeneous.

Expert opinion: We now have many new insights and therapeutic possibilities, but progress hinges on robust data from well-conceived, adequately powered trials. To make this feasible, the field needs a refined, activity-based, heart-specific AMR classification aligned with Banff and validated noninvasive biomarkers (e.g. dd-cfDNA, endothelial-injury markers, NK-activity signatures) to enable early detection, monitoring, and rigorous trial enrollment. Emerging biology positions NK-cell targeting as a leading therapeutic direction. Clinical adoption will depend on reproducible assays, multicenter validation, and standardized reporting.

Background: While clinical trials have demonstrated that approximately 50% of patients with Crohn's disease (CD) maintain clinical remission at 1 year with infliximab (IFX), the outcomes of long-term IFX treatment in CD are still under scrutiny.

Research design and methods: This retrospective cohort study analyzed 113 patients with CD from September 2010 to July 2025 to evaluate adherence and clinical remission rates, as well as to identify factors associated with treatment adherence.

Results: The median duration of IFX treatment was 61.7 months. At the 72-month follow-up (M72), patients were categorized into M72-remission (44.2%) and M72-non-remission (55.8%) groups. The M72-remission group had a significantly higher baseline Crohn's disease activity index score than the M72-non-remission group (p = 0.003). However, this difference was no longer significant at the 72-month follow-up (p = 0.254). At the final follow-up, 67.3% of patients continued to receive IFX treatment. Both the adherence rate to IFX (p = 0.012) and the clinical remission rate (p = 0.030) were significantly higher in patients with no surgery compared to those with surgery prior to IFX treatment.

Conclusions: Early clinical remission was not associated with the adherence to IFX treatment. Previous surgery may be an independent risk factor for long-term IFX treatment failure.

Introduction: Biosimilar stewardship includes safety, appropriate use, and value. However, it faces challenges due to shortages in disproportionality methods. Artificial intelligence (AI) tools have been emerged as practical 'intelligence augmentation' strategies that strengthen, rather than replace, traditional pharmacovigilance (PV) signal management.

Areas covered: We conducted a narrative review with evidence mapping (Jan 2010-Nov 2025) across PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane, citation-chasing, and targeted grey/first-party sources (regulators/HTA portals, PV centers, NHS dashboards, technical documentation). We prioritized biosimilar-specific pharmacovigilance, switching/implementation, and value-tracking evidence; general PV/AI literature was used primarily to describe analytic methods and governance where it directly informs biosimilar-specific problems A study-selection summary is provided for transparency. To improve interpretability for readers, we also include brief 'deployment vignettes' describing how key AI-enabled functions are operationally implemented in routine pharmacovigilance workflows.

Expert opinion: Medium-term priorities include federated, KPI-linked analytics and better external validation and transportability; near-term 'assist' deployments - such as narrative NLP, normalization, de-duplication, and multi-feature ranking under human-in-the-loop governance - can quantifiably improve case completeness, traceability, and triage. To achieve reliable production use, persistent bottlenecks (class imbalance, vocabulary mapping) require clear monitoring and standard assessment procedures.

Introduction: The approval in 2011 of belimumab, the first biologic approved for systemic lupus erythematosus (SLE), paved the way for testing additional biologic agents to expand treatment options for SLE. We discuss new biologic therapies that show promising results and discuss some of the barriers that must be considered in SLE clinical trials.

Areas covered: This review focuses on established and novel biologics targeting the BAFF/APRIL, type-I IFN, CD20, and CD40/CD40 ligand pathways and on CAR-T therapy. We review the relevant clinical trials, focusing on safety and efficacy. A literature search was conducted in PubMed/MEDLINE. Keywords used were "Lupus Erythematosus, Systemic' OR (("Lupus* AND ("Biological Products' OR Biologics*)). These search results were filtered to include only clinical trials. In addition, literature from the authors' personal collections were considered.

Expert opinion: Several novel therapies have shown promising results. The treatment approach for SLE is shifting toward a balanced and targeted immunosuppression tailored to key drivers of SLE pathophysiology and diverse phenotypes. Given the number of agents already or soon-to-be approved, the appropriate therapy for a given patient must be a shared patient-physician decision.

Background: Alzheimer's disease (AD) is the most prevalent cause of dementia and has been closely linked to βSupplemental data for this article can be accessed online at ht tps://doi.org/-amyloid accumulation. However, the efficacy and safety of anti-β-amyloid monoclonal antibodies remain debated.

Methods: We systematically searched PubMed, Embase, and Cochrane databases for RCTs comparing anti-β-amyloid monoclonal antibodies with placebo in early-stage AD. Eligible trials enrolled participants with biomarker-supported AD and reported global, cognitive, or safety outcomes, including the CDR-SB, ADAS-Cog 13/14, ARIA, and brain volumetric measures.

Results: Six RCTs including 7837 participants were analyzed. Mean age ranged from 69.8 to 75.4 years, and 57.4% were APOE ε4 carriers. Anti-β-amyloid therapy was associated with small differences in global and cognitive outcomes, best described as a modest slowing of decline on the CDR-SB and ADAS-Cog scales. Treatment was associated with increased risks of ARIA-E (RR, 9.40; 95% CI, 6.98-12.66) and ARIA-H (RR, 2.40; 95% CI, 2.08-2.78), as well as greater ventricular enlargement and hippocampal atrophy.

Conclusion: In early AD, anti-β-amyloid monoclonal antibodies are associated with modest slowing of decline accompanied by increased ARIA risk and unfavorable structural brain changes, limiting clinical applicability.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD420251071393.