GOPred: GO Molecular Function Prediction by Combined Classifiers

Functional protein annotation is an important matter for in vivo and in silico biology. Several computational methods have been proposed that make use of a wide range of features such as motifs, domains, homology, structure and physicochemical properties. There is no single method that performs best in all functional classification problems because information obtained using any of these features depends on the function to be assigned to the protein. In this study, we portray a novel approach that combines different methods to better represent protein function. First, we formulated the function annotation problem as a classification problem defined on 300 different Gene Ontology (GO) terms from molecular function aspect. We presented a method to form positive and negative training examples while taking into account the directed acyclic graph (DAG) structure and evidence codes of GO. We applied three different methods and their combinations. Results show that combining different methods improves prediction accuracy in most cases. The proposed method, GOPred, is available as an online computational annotation tool (http://kinaz.fen.bilkent.edu.tr/gopred)

Kombinationstherapien in der Immunonkologie: Differenzierte regulatorische Herangehensweisen

Combination therapies of different drugs are an integral part of medicine. However, there is a scientific and regulatory need to understand the contribution of each drug to the overall effect, i.e., nonclinical and clinical development programs have to consider these aspects and need to be designed accordingly. Many drugs are currently under development that attempt to control malignant diseases in the long term by using and activating components of the patient's own immune system. The term immuno-oncology is often used in this context. Medicines that are developed and used for immuno-oncology can be assigned to completely different classes of medicines.This article provides an analysis of combination therapies in immuno-oncology with medicinal products produced by biotechnological manufacturing. This encompasses checkpoint inhibitors, genetically modified cell therapies, tumor vaccines, and oncolytic viruses. The challenges in clinical development are demonstrated on the basis of this heterogenous group of approved immuno-oncological drugs that have been investigated in combination therapies. Due to the different characteristics and number of combination partners, an individually tailored program must be designed for each development program and there is no standard solution

The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Tafasitamab is a humanized monoclonal antibody that binds to the CD19 antigen, which is expressed in tumor cells from patients with diffuse large B-cell lymphoma (DLBCL). On June 24, 2021, a positive opinion for a conditional marketing authorization was issued by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) for tafasitamab, in combination with lenalidomide, for the treatment of adult patients with relapsed or refractory DLBCL who are ineligible for autologous stem cell transplantation. Tafasitamab was evaluated in the phase 2 single-arm, multicenter, open-label L-MIND clinical trial. The primary endpoint of this trial was objective response rate (ORR). The best ORR, achieved at any time during the study, was 56.8% (95% confidence interval: 45.3%–67.8%), and the median duration of response was 34.6 months (95% confidence interval: 26.1–not reached). The most frequently reported adverse events by system organ class were infections and infestations (72.8%; grade ≥3: 29.6%), blood and lymphatic system disorders (65.4%; grade ≥3: 56.8%), gastrointestinal disorders (64.2%; grade ≥3: 2.5%), and general disorders and administration site conditions (58.0%; grade ≥3: 8.6%). The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the CHMP

The changing landscape of treatment options in childhood acute lymphoblastic leukaemia

New paediatric acute lymphoblastic leukaemia (ALL) treatments have been developed and innovative products are in the pipeline. However, despite many active clinical trials, bridging bench science to clinical development to authorised medicines remains challenging. Research in first-line treatment continues to focus on multidrug chemotherapy with the potential addition of new targeted molecules being studied. Research in second- and third-line treatment represents a shift from cytotoxic intensification to an area of precision medicine through emergent innovative and immuno-oncology products. The collaborative research model in ALL involving different stakeholders should intensify to facilitate bench-to-bedside clinical translation for the benefit of patients