It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has ...dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Antitumor rejection by the immune system is a complex process that is regulated by several factors. Among these factors are the quality and quantity of mutational events that occur in cancer cells. ...Perhaps one of the most important types of mutations that influence antitumor immunity is the neoantigen, that is, a non-self-antigen that arises as a result of somatic mutation. Recent work has demonstrated that neoantigens hold significant promise for developing new diagnostic and therapeutic modalities. Therapeutic targeting of neoantigens is important for achieving benefit following therapy with immune checkpoint blockade agents or for cancer vaccines targeting mutations. Here, we review our understanding of neoantigens and discuss new developments in the quest to use them in cancer immunotherapy.
Neoantigens are antigens generated by somatic mutations that can be recognized by the host immune system.
Neoantigens in tumors can be targeted by T cells.
Neoantigens can be identified and used in cancer therapies, such as cancer vaccines.
Confidence intervals for the mean of discrete exponential families are widely used in many applications. Since missing data are commonly encountered, the interval estimation for incomplete data is an ...important problem. The performances of the existing multiple imputation confidence intervals are unsatisfactory. We propose modified multiple imputation confidence intervals to improve the existing confidence intervals for the mean of the discrete exponential families with quadratic variance functions. A simulation study shows that the coverage probabilities of the modified confidence intervals are closer to the nominal level than the existing confidence intervals when the true mean is near the boundaries of the parameter space. These confidence intervals are also illustrated with real data examples.
The current commercial plastic manufactures have been produced using petroleum-based resource. However, due to concerns over the resource depletion and the environmental sustainability, ...bioresource-based manufacturing processes have been developed to cope against these concerns. Bioresource-derived 2,5-furandicarboxylic acid (FDCA) can be utilized as a building block material for plastic manufactures. To date, numerous technologies have been developed for the production of FDCA using various types of bio-based feedstocks such as hydroxymethylfurfural (HMF), 6-C sugars, and polysaccharides. The commercial companies produce FDCA using HMF-based production processes due to their high production efficiency, but the high price of HMF is a problem bottleneck. Our review affords important information on breakthrough approaches for the cost-efficient and sustainable production of FDCA using raw plant feedstocks rich in inulin. These approaches include bioprocessing technology based on the direct use of raw plant feedstocks and biomodification of the target plant sources. For the former, an ionic liquid-based processing system is proposed for efficient pretreatment of raw plant feedstocks. For the latter, the genes encoding the key enzymes; sucrose:sucrose 1-fructoyltransferase (1-SST), fructan:fructan 1-fryuctosyltransferase (1-FFT), fructan 1-exohydrolase (1-FEH), and microbe-derived endoinulinase, are introduced for biomodification conducive to facilitating bioprocess and improving inulin content. These approaches would contribute to cost-efficiently and sustainably producing bio-based FDCA.
Chemical manufacturing involves carbon sources releasing CO2 into the atmosphere. By contrast, seaweeds are carbon sinks that can absorb released CO2 and therefore have great potential for use as ...feedstocks in sustainable chemical manufacturing. In particular, seaweeds could contribute to mitigating vast amounts of global CO2 emissions. Accordingly, seaweeds could be an excellent candidate biomaterial for sustainable production of hydroxymethylfurfural (HMF), called a ‘sleeping giant’ platform chemical due to its wide versatility in chemical manufacturing. HMF is produced through sugar dehydration mechanisms, and seaweed storage glucans comprised of glucose can be appropriate feeding substrates for its production. This opinion article introduces a new opportunity for sustainable production of HMF using storage glucan-rich seaweeds.
Raw seaweeds rich in storage glucans could be optimal biomaterials for sustainable production of HMF.Seaweed-based bioprocesses could contribute to reducing CO2 emissions released from the chemical industry.A biostrategy for enhancing seaweed growth could help to reduce HMF production costs.A biostrategy for augmenting storage glucans of seaweeds could apply to other algal species.A conversion technology of algal storage glucans could be applicable for the production of HMF from other similar bio-based polymers.
Marine plants, including macroalgae and seagrass, show promise as biorenewable feedstocks for sustainable chemical manufacturing. This study explores their potential in producing ...2,5-furandicarboxylic acid (FDCA), a versatile platform chemical for commodity polymers. FDCA-based polyethylene 2,5-furandicarboxylate offers a sustainable alternative to petroleum-derived polyethylene terephthalate, commonly used in plastic bottles. Our research pioneers the concept of a marine plant-based FDCA biorefinery, introducing innovative approaches for sustainability and cost-effectiveness. This review outlines the use of ionic liquid-based solvents (ILS) and deep eutectic solvent (DES) systems in FDCA production. Additionally, we propose biomodification strategies involving target enzyme-encoding genes to enhance the depolymerization of non-structural storage glucans in marine plants. Our findings pave the way for eco-friendly biorefineries and biorenewable plastics.
A microorganism hydrolyzing rice hull was isolated from soil and identified as
Bacillus amyloliquefaciens by analysis of 16S rDNA and partial sequences of the
gyrA gene, and named as
B. ...amyloliquefaciens DL-3. With the analysis of SDS–PAGE, the molecular weight of the purified cellulase was estimated to be 54
kDa. The purified cellulase hydrolyzed avicel, caboxymethylcellulose (CMC), cellobiose, β-glucan and xylan, but not
p-Nitrophenyl-β-
d-glucopyranoside (PNPG). Optimum temperature and pH for the CMCase activity of the purified cellulase were found to be 50
°C and pH
7.0, respectively. The CMCase activity was inhibited by some metal ions,
N-bromosuccinimide and EDTA in the order of Hg
2+
>
EDTA
>
Mn
2+
>
N-bromosuccinimide
>
Ni
2+
>
Pb
2+
>
Sr
2+
>
Co
2+
>
K
+. The open reading frame of the cellulase from
B. amyloliquefaciens DL-3 was found to encode a protein of 499 amino acids. The deduced amino acid sequence of the cellulase from
B. amyloliquefaciens DL-3 showed high identity to cellulases from other
Bacillus species, a modular structure containing a catalytic domain of the glycoside hydrolase family 5 (GH5), and a cellulose-binding module type 3 (CBM3).
Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have ...better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO).
We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded.
A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 95% CI 1.214-4.314, p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 95% CI 1.018-1.104, p = 0.005) or MP referenced to PBW (HR 1.004 95% CI 1.002-1.007, p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H
O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H
O) (63.6% vs. 29.7%, p < 0.001).
MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.
Based on their environmental benefits, microalgae are currently the most favorable renewable biofeedstock materials for biodiesel production. However, the possibility of an economically viable ...production system using microalgae is still technology-driven, not yet market-driven due to its higher production cost. Accordingly, to establish industrial manufacturing systems for microalgal biodiesel, it is critical to develop technology for its cost-effective production. Here, we propose some novel molecular strategies, which have not been attempted for microalgal biodiesel production and are conducive to cost-effective production of biodiesel from microalgae. These include genetic manipulation strategies for higher biomass yield and extracellular production of free fatty acids, triacylglycerol, and fatty acid ethyl ester (biodiesel) with high quality, which could be exploited as a breakthrough technology for the cost-efficient production of microalgal biodiesel.
Unlike petrorefinery, biorefinery uses carbon-based biomaterials, such as plant feedstocks, as the major feeding input materials in chemical manufacturing. To date, petroleum-based resources have ...been used for the production of wide spectrums of chemical products. However, petrorefinery is currently associated with a variety of issues, i.e., concerns over adverse impacts on the environment and human society. As an alternative technology, the sustainable biorefinery is a matter of great importance in industrial chemical manufacturing due primarily to its sustainability. As carbon-based resources, plants are paramount biomaterials for biorefinery process required in sustainable chemical manufacturing. In particular, raw plant-based biorefinery is a breakthrough technology for chemical manufacturing due mainly to its sustainable benefits. Nowadays, numerous biorefinery technologies have been developed for the production of industrially valuable chemicals. HMF, a versatile platform chemical, can be produced by dehydrating hexose sugars using raw plant feedstocks such as inulin-rich, starch-rich, and lignocellulosic plants and now, it is generally recognized as a chemical feedstock for future chemical manufacturing and bioenergy production. In this review article, this emerging hybrid technology is discussed in relation to the production of HMF from raw plant feedstocks mentioned above. In addition, the plant candidates useful for biorefinery processing of raw plant feedstocks are introduced and bioengineering strategy for their genetic modification is together described to provide current knowledge on sustainable biorefinery.
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