Expert Opinion on Biological Therapy最新文献

Introduction: Natural killer (NK) cells are innate immune effectors that can eliminate malignant cells without prior sensitization. By recognizing cellular stress signals and releasing inflammatory mediators, they contribute to immune surveillance and regulation. Their therapeutic potential lies in their ability to act across donor barriers with a reduced risk of graft-related complications; however, clinical translation remains challenging due to tumor immune evasion and limited persistence in suppressive environments.

Areas covered: This review summarizes the biological roles of NK cells in cancer immunity and examines recent therapeutic approaches that harness their cytotoxic and regulatory properties. We discuss barriers to clinical application, including immune suppression, antigen loss, and manufacturing limitations. In addition, we highlight emerging strategies, such as gene editing, rational combination therapies, and standardized clinical trial designs, aimed at improving therapeutic efficacy.

Expert opinion: NK cell-based therapies represent a promising avenue in cancer immunotherapy but require carefully designed solutions to overcome their inherent limitations. Advances in biomarker-guided patient selection, integration with existing treatment modalities, and international collaboration will be critical for translating NK cell biology into effective and durable clinical outcomes.

Introduction: The antibody therapeutic landscape has been dominated by monoclonal antibodies (mAbs) since the early 2000s, leading to polyclonal antibodies (pAbs) assuming a less prominent role in clinical use. However, the multiepitope targeting capability of pAbs has generated renewed interest over the last five years. Emerging technologies such as recombinant antibody pools are prompting a revisit of the distinction between traditional mAb and pAb therapies.

Areas covered: Using listed FDA-approved polyclonal therapies as a basis for our literature searches, we explore the applications of current pAb therapies and examine whether mAbs may eventually replace them. We also discuss the costs and cost-effectiveness of directly competing mAb and pAb therapies for a variety of clinical indications. Finally, we review emerging technologies, such as glyco-humanized and recombinant pAbs, covering their modes of action, manufacturing approaches, and current clinical trial statuses.

Expert opinion: The current clinical pAb therapy landscape is varied, evolving, and continues to be challenged by mAbs. For the pAb therapies explored in this review, multiple competing mAb alternatives are progressing toward clinical approval. Future hybrid technologies like recombinant pAbs may allow multiple epitope targeting while achieving enhanced safety profiles and batch-to-batch consistency; however, their cost-effectiveness remains uncertain.

Objective: To evaluate indications, clinical response, outcomes, and tolerability of intravenous immunoglobulin (IVIG) therapy in patients with juvenile dermatomyositis (JDM) in a multicenter cohort.

Methods: This retrospective multicenter study included 29 patients with JDM who received IVIG. Demographic data, clinical features, laboratory parameters, and standardized disease activity scores were recorded at disease onset, before and after IVIG treatment, and at final follow-up. Treatment response and adverse events were analyzed.

Results: IVIG was initiated a median of 1.2 months (IQR: 0.1-18.9) after diagnosis and continued for a median of 8.2 months (IQR: 5.6-21.6). Indications included refractory muscle weakness, persistent skin disease, calcinosis, and interstitial lung disease (ILD). IVIG therapy was associated with significant improvements in disease activity measures and laboratory parameters (p < 0.001). Calcinosis partially or completely resolved in 3 of 6 patients, while no change was observed in the single ILD case. IVIG was well tolerated, with only mild adverse effects.

Conclusion: IVIG appears to be a safe and effective treatment option for JDM, particularly in refractory or skin-predominant disease. Although causal inferences are limited by the retrospective design and the absence of a control group, these real-world findings support the inclusion of IVIG in an individualized treatment approach.

Background: To evaluate early real-world clinical outcomes on the safety and efficacy of the ranibizumab biosimilar (Oceva, Sun Pharmaceuticals, India).

Research design and methods: A multicenter, retrospective, uncontrolled observational study evaluating data from 404 eyes that received a total of 742 intravitreal injections of the ranibizumab biosimilar (Oceva 0.5 mg) across four centers in India, administered between August 2024 and May 2025 in variable approved and off label indications. Of the total eyes, 288 were treatment-naïve naïve, while 116 eyes were previously treated.

Results: The mean (SD) follow-up was 14.39 ± 12.5 weeks. The mean BCVA improved significantly from 0.87 to 0.59 LogMAR (p < 0.0001; d = 0.61), and mean CFT reduced from 406.8 µm to 306.5 µm (p < 0.0001; d = 0.66). Naïve eyes showed greater improvements than previously treated ones. No serious ocular or systemic adverse events were observed.

Conclusions: The preliminary real-world data from this limited early series suggest that ranibizumab biosimilar (Oceva) appears to be efficacious and safe across the approved indications. However, long-term data with a larger population are needed to further strengthen the findings of this study.

Background: Biologic agents have significantly improved psoriasis treatment, but patient responses exhibit considerable heterogeneity, highlighting the urgent need for practical predictive biomarkers of therapeutic efficacy.

Research design and methods: This prospective cohort study enrolled 422 psoriasis patients and 150 healthy controls. Sixteen CPD parameters were measured using a hematology analyzer. We analyzed associations between baseline CPD and disease severity as well as inflammatory markers, assessed their predictive value for treatment response over 48 weeks of biologic therapy, and monitored early dynamic changes in CPD and their relationship with treatment response in 169 patients.

Results: All CPD parameters were significantly elevated in psoriasis patients compared to healthy controls (all p < 0.001). Baseline mean lymphocyte volume (MN-V-LY) demonstrated sustained negative correlations with PASI improvement rates from weeks 4 to 48 (ρ = -0.278 to -0.449, all p < 0.001). Early reduction in monocyte volume heterogeneity (SD-V-MO) was significantly associated with long-term efficacy (ρ = -0.355 to -0.546, all p < 0.001).

Conclusions: As simple, standardized hematological parameters, CPD show potential for clinical application in predicting biologic therapy response in psoriasis.

Introduction: Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN) are aggressive hematologic malignancies with poor outcomes, particularly in relapsed/refractory settings. CD123, the interleukin-3 receptor alpha chain, is highly expressed on leukemic blasts and leukemia stem cells, making it an attractive therapeutic target with limited expression on normal hematopoietic cells. CD123-directed therapies - including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and CAR T-cell therapies - are under active investigation.

Areas covered: This review details the preclinical rationale, clinical development, efficacy, and toxicity of CD123-targeted therapies. It discusses completed and ongoing clinical trials for agents such as tagraxofusp, pivekimab sunirine, flotetuzumab, vibecotamab, and investigational CAR T-cell therapies (e.g. MB-102, UCART123v1.2). Toxicities, including myelosuppression, cytokine release syndrome (CRS), and hepatotoxicity - are characterized in detail, with attention to mitigation strategies. Future directions highlight combination regimens, switchable CAR designs, and biomarker-driven personalization.

Expert opinion: CD123-targeted therapy represents a promising yet challenging frontier in treating high-risk leukemias. While clinical activity has been demonstrated, especially in BPDCN, therapeutic durability and safety remain hurdles. Precision in antigen targeting, combination strategies, and toxicity management will be critical for successful integration of CD123-directed therapies into standard clinical practice.

Introduction: Small-cell lung cancer (SCLC) is a rapidly progressive form of cancer often expressing DLL3. Tarlatamab is a bispecific antibody which blocks DLL3-related downstream pathways and activates antitumor host immunity. It is currently authorized in the U.S.A. for the treatment of extensive SCLC.

Areas covered: This is a review evaluating the basic pharmacology and clinical data regarding tarlatamab. Most data come from SCLC; in the other two diseases, tarlatamab is in early clinical development.

Expert opinion: Tarlatamab is an effective therapy mainly in relapsed/progressed SCLC, and its assessment in limited SCLC alone or combined with other therapies is supported by the existing data.