Recent advances and current challenges in CAR-T cell therapy.

Rapid advancements in the field of immunotherapy have significantly improved cancer treatments. Specifically, an individualized cell-based modality which involves the removal of some of the patient's own white blood cells, including T cells, has revolutionized research in this field. This study focuses on the recent advances and current challenges of Chimeric Antigen Receptor- T (CAR-T) cell therapy and its regulations in the United States (US) and European Union (EU). Understanding the regulatory regimes of CAR-T cell therapy is critical for researchers and manufacturers as they navigate the hurdles of bringing CAR-T cell therapy to the global market. Benefits of CAR-T cell therapy include high response rates and the potential of long-term remissions in some haematological malignancies. However, the drawbacks are still evident including high costs, adverse reactions, and limited efficacy to solid tumours. CAR-T cell therapy is rapidly advancing, with 1231 clinical trials launched globally according to www.clinicalTrial.gov . The future of CAR-T cell therapy holds enormous promise but improving its safety, effectiveness, and availability are still barriers to its successful implementation.

Current trends in biopharmaceuticals production in Escherichia coli.

Since the manufacture of the first biotech product for a fledgling biopharmaceutical industry in 1982, Escherichia coli, has played an important role in the industrial production of recombinant proteins. It is now 40 years since the introduction of Humulin® for the treatment of diabetes. E. coli remains an important production host, its use as a cell factory is well established and it has become the most popular expression platform particularly for non-glycosylated therapeutic proteins. A number of significant inherent obstacles in the use of prokaryotic expression systems to produce biologics has always restricted production. These include codon usage, the absence of post-translational modifications and proteolytic processing at the cell envelope. In this review, we reflect on the contribution that this model organism has made in the production of new biotech products for human medicine. This will include new advancements in the E. coli expression system to meet the biotechnology industry requirements, such as novel engineered strains to glycosylate heterologous proteins, add disulphide bonds and express complex proteins. The biopharmaceutical market is growing rapidly, with two production systems competing for market dominance: mammalian cells and microorganisms. In the past 10 years, with increased growth of antibody-based therapies, mammalian hosts particularly CHO cells have dominated. However, with new antibody like scaffolds and mimetics emerging as future proteins of interest, E. coli has again the opportunity to be the selected as the production system of choice.

A randomized controlled trial of the effect of increased intravenous hydration on the course of labor in nulliparous women.

OBJECTIVE: One variable that has the potential to affect the course of labor but has not been evaluated previously is the adequacy of maternal hydration. Typical orders provide for 125 mL of intravenous fluids per hour in patients taking limited oral fluids. Many such patients are clinically dehydrated. Physiologists have shown that increased fluids improve skeletal muscle performance in prolonged exercise. This study was designed to determine whether increased intravenous fluids affect the progress of labor. STUDY DESIGN: Nulliparous women with uncomplicated singleton gestations at term, in spontaneous active labor with dilatation between 2 and 5 cm, and with a cephalic presentation were included. Patients who gave consent were randomly selected to receive either 125 mL or 250 mL of intravenous fluids per hour. RESULTS: One hundred ninety-five patients were randomly selected, 94 to the 125-mL group and 101 to the 250-mL group. Prerandomization variables were well matched between the 2 groups. The mean volume of total intravenous fluids was significantly greater in the 250-mL group (2008 mL vs 2487 mL; P =.002), as was the mean hourly rate (152 mL/h in the 125-mL group vs 254 mL/h in the 250-mL group; P =.001). The frequency of labor lasting >12 hours was statistically higher in the 125-mL group (20/78 [26%] vs 12/91 [13%]; P =.047). In addition, there was a trend favoring longer mean duration of the first stage and total duration of labor in patients delivered vaginally in the 125-mL group, by 70 and 68 minutes, respectively (P =.06). There was a trend toward a lower frequency of oxytocin administration for inadequate labor progress in the higher fluid rate group (61 [65%] in the 125-mL group vs 51 [49%] in the 250-mL group; P =.06). Cesarean deliveries were more frequent in the 125-mL group (n = 16) than in the 250-mL group (n = 10) but did not reach statistical significance. CONCLUSION: This study presents the novel finding that increasing fluid administration for nulliparous women in labor above rates commonly used is associated with a lower frequency of prolonged labor and possibly less need for oxytocin. Thus inadequate hydration in labor may be a factor contributing to dysfunctional labor and possibly cesarean delivery. Consideration of this factor in clinical management and in future studies considering variables that affect labor is warranted.