Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma.

Follicular lymphoma (FL) is the most common indolent lymphoma. Since the advent of rituximab, FL has seen a progressive improvement in patient prognosis. While chemotherapy combined with an anti-CD20 monoclonal antibody remains standard first-line therapy, most patients will relapse and require subsequent therapy. T-cell-redirecting therapies can be very potent and are transforming the therapeutic landscape in the relapsed and refractory (R/R) setting. T-cell-dependent bispecific antibodies, of which mosunetuzumab is the first to be approved for R/R FL, are proving to be a highly effective, 'off-the-shelf' option with manageable toxicities. This review covers approved treatments for R/R FL and focuses on preclinical and clinical data available for mosunetuzumab (Lunsumio™), with the goal of determining its role in the treatment of R/R FL.

Follicular lymphoma (FL) is a common and often slowly progressing cancer of B cells, a component of the immune system. While FL is not considered curable, patients' survival has improved significantly over the last 15 years owing to the addition of new treatments like rituximab (an immunotherapy) and bendamustine (a chemotherapy drug) to the list of available therapies. However, FL patients often experience disease recurrences and need several courses of therapy during their lifetime. In the last 10 years the understanding of how T cells ­ a key part of the body's natural defense against disease ­ can help kill cancerous cells has grown tremendously, leading to the development of highly effective treatments that harness these T cells to kill cancer cells. Mosunetuzumab, one such therapy, is an antibody that can bind both the T cells and the cancerous B cells of FL. Bringing the T cell to the cancerous B cell causes T-cell activation and killing of the lymphoma. It has proven highly effective, and mosunetuzumab has recently been approved in Europe and the USA for the treatment of recurrent FL. This review focuses on the design and testing of mosunetuzumab in the laboratory and in patients, and explains its mode of action and potential role in the treatment of relapsed/refractory FL.

Attributes of Physical Activity and Gut Microbiome in Adults: A Systematic Review.

Growing evidence shows the contribution of physical activity interventions to the gut microbiome. However, specific physical activity characteristics that can modify the gut microbiome are unknown. This review's aim was to explore the contribution of physical activity intervention characteristics on human gut microbiome composition, in terms of diversity, specific bacterial groups, and associated gut microbiome metabolites. A literature search in PubMed; Cochrane Library; CINAHL-EBSCO; SCOPUS; Web of Science; ClinicalTrials.gov; PROSPERO; and ProQuest. Five studies met the inclusion criteria of a physical activity intervention duration of at least five weeks, with any description of the type or dose used. All included studies reported an endurance training; two studies used endurance and an additional muscle-strengthening training regimen. All studies reported using a dietary intervention control. Reported gut microbiome α-diversity changes were non-significant, ß-diversity changes were mixed (three studies reported an increase, two reported non-significant changes). All studies reported significant changes in the abundances of specific bacterial/archaea groups and bacteria-related metabolites following interventions. In conclusion, physical activity (regardless of specific characteristics) has significant contribution to gut microbiome composition and associated metabolites. There are no current recommendations for physical activity to promote gut microbiome composition. Future studies should focus on the contribution of current recommended physical activity dose to gut microbiome composition.

Oxidative markers in cryopreservation medium from frozen-thawed embryos: a possible tool for improved embryo selection in in vitro fertilization?

PURPOSE: The present study evaluated the association between oxidative parameters in embryo cryopreservation medium and laboratory and clinical outcomes. METHODS: This prospective laboratory study was conducted in an IVF unit in a university-affiliated hospital with 91 IVF patients undergoing a frozen-thawed embryo transfer cycle. Following thawing, 50 µL of embryo cryopreservation medium was retrieved from each cryotube and tested by the thermochemiluminescence (TCL) assay. TCL amplitudes after 50 (H1), 150 (H2), and 280 s (H3) were recorded in counts per second (CPS) and the TCL ratio determined for comparison with implantation and pregnancy rates. RESULTS: A total of 194 embryos were transferred in 85 frozen-thaw cycles. Twenty-one pregnancies (24.7 %) occurred. Implantation and overall and clinical pregnancy rates were higher when the median TCL H1 amplitude was <32 CPS compared to ≥32 CPS (14.6 vs. 5.3 %, 37.5 vs. 17 %, 28.1 vs. 9.4 %, respectively). No pregnancies occurred when the H1 amplitude was ≥40 CPS. Logistic regression multivariate analysis found that only the median TCL H1 amplitude was associated with the occurrence of pregnancy (OR = 2.93, 95 % CI 1.065-8.08). The TCL ratio inversely correlated with the duration of embryo cryopreservation (r = -0.37). CONCLUSIONS: The results indicate that thawed embryos may express oxidative processes in the cryopreservation medium, and higher oxidative levels are associated with lower implantation rates. These findings may aid in the improved selection of frozen-thawed embryos for IVF.