Expert Opinion on Biological Therapy最新文献

Introduction: Immunochemotherapy with PD-1 blockade has been established as the current standard first-line therapy for patients with mGEA. Reviewing the history of clinical trials offers valuable insight into the evolution of immune oncology in mGEA, paving the way for future advancements in this field.

Areas covered: This review summarizes the findings of previous clinical trials related to immunotherapy for patients with GEA in the metastatic and locally advanced setting. We also introduce ongoing clinical trials to address the current challenging issues in clinical practice.

Expert opinion: In general, GEA exhibits intermediate immunogenic characteristics with heterogeneous expressions, and responders to anti-PD-(L)1 therapy are mostly enriched to patients with specific genomic profiles such as MSI-H, high PD-L1 expression, high TMB, and EBV-associated type. Co-administration with anti-angiogenic agents or simultaneous blockade of immune checkpoint molecules is being explored to offer benefit of immunotherapy for more patients. We hope that CLDN18.2 and upcoming targets like FGFR2b will complement the treatment niche of immunotherapy in the field of mGEA. Bispecific antibodies, antibody drug conjugates, CAR-T, and vaccine are anticipated to enhance efficacy and expand the scope of immunotherapy.

Introduction: As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing.

Areas covered: Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions.

Expert opinion: There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.

Introduction: Cell therapy development represents a critical challenge in amyotrophic lateral sclerosis (ALS) research. Despite more than 20 years of basic and clinical research, no definitive safety and efficacy results of cell-based therapies for ALS have been published.

Areas covered: This review summarizes advances using stem cells (SCs) in pre-clinical studies to promote clinical translation and in clinical trials to treat ALS. New technologies have been developed and new experimental in vitro and animal models are now available to facilitate pre-clinical research in this field and to determine the most promising approaches to pursue in patients. New clinical trial designs aimed at developing personalized SC-based treatment with biological endpoints are being defined.

Expert opinion: Knowledge of the basic biology of ALS and on the use of SCs to study and potentially treat ALS continues to grow. However, a consensus has yet to emerge on how best to translate these results into therapeutic applications. The selection and follow-up of patients should be based on clinical, biological, and molecular criteria. Planning of SC-based clinical trials should be coordinated with patient profiling genetically and molecularly to achieve personalized treatment. Much work within basic and clinical research is still needed to successfully transition SC therapy in ALS.

Introduction: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture non-union. Non-union is generally believed to develop due to inadequate fixation, underlying host-related factors, or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of non-union.

Areas covered: This review provides a detailed description of non-union from a clinical perspective, including the state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical, and infection research fields are presented, including the latest in smart implants, osteoinductive materials, and in silico modeling.

Expert opinion: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis, and treatment of non-union. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of non-union causes and correlations, leading to the development of more effective treatments.