scholarly journals Plants as alternative platforms for monoclonal antibodies productions.

Author(s):  
Natalia Glumińska ◽  
Magdalena Krzesłowska

Monoclonal antibodies (mAbs) are widely used in medical therapy and diagnostics, veterinary therapy, and research. The demand for mAbs reaches several dozen tons per year and is constantly growing, approaching the limits of current production possibilities. Mammalian expression systems, which currently dominate the bioproduction industry, have limited production capacity and require high capital investment and production costs. Plants are becoming promising expression platforms due to their scalability, speed, low cost of production, low risk of contamination from animal pathogens and eukaryotic mechanisms of post-translational protein modification. The transgenic plants used for the production of mAbs can be obtained by stable transformation of plant cells as well as transient expression of foreign proteins. In this review, we extract a broad overview of articles, many of them from recent years, concerning modern approaches to producing monoclonal antibodies in plants, methods for modifying the carbohydrate profile of mAbs, and purifying the resulting product. We also present current data on the practical use of mAbs in medical therapies and potential methods of producing antibodies on a very large scale, able to meet the future market demand.

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea Crosino ◽  
Elisa Moscato ◽  
Marco Blangetti ◽  
Gennaro Carotenuto ◽  
Federica Spina ◽  
...  

AbstractShort chain chitooligosaccharides (COs) are chitin derivative molecules involved in plant-fungus signaling during arbuscular mycorrhizal (AM) interactions. In host plants, COs activate a symbiotic signalling pathway that regulates AM-related gene expression. Furthermore, exogenous CO application was shown to promote AM establishment, with a major interest for agricultural applications of AM fungi as biofertilizers. Currently, the main source of commercial COs is from the shrimp processing industry, but purification costs and environmental concerns limit the convenience of this approach. In an attempt to find a low cost and low impact alternative, this work aimed to isolate, characterize and test the bioactivity of COs from selected strains of phylogenetically distant filamentous fungi: Pleurotus ostreatus, Cunninghamella bertholletiae and Trichoderma viride. Our optimized protocol successfully isolated short chain COs from lyophilized fungal biomass. Fungal COs were more acetylated and displayed a higher biological activity compared to shrimp-derived COs, a feature that—alongside low production costs—opens promising perspectives for the large scale use of COs in agriculture.


2021 ◽  
Vol 14 (7) ◽  
pp. 700
Author(s):  
Theodoros Mavridis ◽  
Christina I. Deligianni ◽  
Georgios Karagiorgis ◽  
Ariadne Daponte ◽  
Marianthi Breza ◽  
...  

Now more than ever is the time of monoclonal antibody use in neurology. In headaches, disease-specific and mechanism-based treatments existed only for symptomatic management of migraines (i.e., triptans), while the standard prophylactic anti-migraine treatments consist of non-specific and repurposed drugs that share limited safety profiles and high risk for interactions with other medications, resulting in rundown adherence rates. Recent advances in headache science have increased our understanding of the role of calcitonin gene relate peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) pathways in cephalic pain neurotransmission and peripheral or central sensitization, leading to the development of monoclonal antibodies (mAbs) or small molecules targeting these neuropeptides or their receptors. Large scale randomized clinical trials confirmed that inhibition of the CGRP system attenuates migraine, while the PACAP mediated nociception is still under scientific and clinical investigation. In this review, we provide the latest clinical evidence for the use of anti-CGRP in migraine prevention with emphasis on efficacy and safety outcomes from Phase III and real-world studies.


Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 463
Author(s):  
Mariusz Sikora ◽  
Albert Stec ◽  
Magdalena Chrabaszcz ◽  
Aleksandra Knot ◽  
Anna Waskiel-Burnat ◽  
...  

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.


Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 462
Author(s):  
Houssame Boujjat ◽  
Sylvain Rodat ◽  
Stéphane Abanades

Solar biomass gasification is an attractive pathway to promote biomass valorization while chemically storing intermittent solar energy into solar fuels. The economic feasibility of a solar gasification process at a large scale for centralized H2 production was assessed, based on the discounted cash-flow rate of return method to calculate the minimum H2 production cost. H2 production costs from solar-only, hybrid and conventional autothermal biomass gasification were evaluated under various economic scenarios. Considering a biomass reference cost of 0.1 €/kg, and a land cost of 12.9 €/m2, H2 minimum price was estimated at 2.99 €/kgH2 and 2.48 €/kgH2 for the allothermal and hybrid processes, respectively, against 2.25 €/kgH2 in the conventional process. A sensitivity study showed that a 50% reduction in the heliostats and solar tower costs, combined with a lower land cost of below 0.5 €/m2, allowed reaching an area of competitiveness where the three processes meet. Furthermore, an increase in the biomass feedstock cost by a factor of 2 to 3 significantly undermined the profitability of the autothermal process, in favor of solar hybrid and solar-only gasification. A comparative study involving other solar and non-solar processes led to conclude on the profitability of fossil-based processes. However, reduced CO2 emissions from the solar process and the application of carbon credits are definitely in favor of solar gasification economics, which could become more competitive. The massive deployment of concentrated solar energy across the world in the coming years can significantly reduce the cost of the solar materials and components (heliostats), and thus further alleviate the financial cost of solar gasification.


Agriculture ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 494
Author(s):  
Riccardo Lo Bianco ◽  
Primo Proietti ◽  
Luca Regni ◽  
Tiziano Caruso

The objective of fully mechanizing olive harvesting has been pursued since the 1970s to cope with labor shortages and increasing production costs. Only in the last twenty years, after adopting super-intensive planting systems and developing appropriate straddle machines, a solution seems to have been found. The spread of super-intensive plantings, however, raises serious environmental and social concerns, mainly because of the small number of cultivars that are currently used (basically 2), compared to over 100 cultivars today cultivated on a large scale across the world. Olive growing, indeed, insists on over 11 million hectares. Despite its being located mostly in the Mediterranean countries, the numerous olive growing districts are characterized by deep differences in climate and soil and in the frequency and nature of environmental stress. To date, the olive has coped with biotic and abiotic stress thanks to the great cultivar diversity. Pending that new technologies supporting plant breeding will provide a wider number of cultivars suitable for super-intensive systems, in the short term, new growing models must be developed. New olive orchards will need to exploit cultivars currently present in various olive-growing areas and favor increasing productions that are environmentally, socially, and economically sustainable. As in fruit growing, we should focus on “pedestrian olive orchards”, based on trees with small canopies and whose top can be easily reached by people from the ground and by machines (from the side of the top) that can carry out, in a targeted way, pesticide treatments, pruning and harvesting.


2001 ◽  
Vol 114 (1) ◽  
pp. 187-197 ◽  
Author(s):  
C. Unsold ◽  
M. Hyytiainen ◽  
L. Bruckner-Tuderman ◽  
J. Keski-Oja

Latent TGF-beta binding proteins (LTBPs) are components of the extracellular matrix (ECM). They belong to the fibrillin/LTBP-superfamily, and are high molecular weight glycoproteins characterized by EGF-like repeats and 8-Cys repeats. Most LTBPs associate with the small latent forms of TGF-beta. Their roles include to facilitate the secretion of latent TGF-beta and to target it to the ECM. In order to identify new matrix-binding domains of LTBP-1 and to characterize their association with the extracellular matrix, we have produced (in a mammalian expression system) partly overlapping recombinant fragments of its shorter form, LTBP-1S, and analyzed the binding of the purified fusion proteins to extracellular matrices of cultured human dermal and lung fibroblasts. Recombinant fragments from three different regions of the N- and C-termini showed affinity to the matrix. These interacting regions contain either the first (hybrid), second or fourth 8-Cys domains of the LTBP-1S molecule. They bound independently to the matrix. Each of them had an ability to inhibit the association of native exogenous LTBP-1 with fibroblast extracellular matrix. The interactions of the LTBP-1 fragments with the extracellular matrix resisted treatment with sodium deoxycholate, suggesting strong, possibly covalent binding. The binding occurred in a time- and dose-dependent fashion. The N-terminal fragments bound more readily to the matrices. With all fragments the binding took place both with intact fibroblast matrices and with matrices isolated by sodium deoxycholate. When using CHO cell layers, which form sparse matrices, only the N-terminal fragment of LTBP-1 was efficiently incorporated. The association of the binding fragments with isolated matrices was enhanced by soluble, cell-derived factors. The current data suggest that LTBP-1 contains three different domains with an ability to associate with the extracellular matrix.


Author(s):  
К.Н. Привалова ◽  
Р.Р. Каримов

Исследования по определению энергетической эффективности пастбищных систем со злаковыми и бобово-злаковыми травостоями проведены в Федеральном научном центре кормопроизводства и агроэкологии им. В. Р. Вильямса. В статье приведены результаты агроэнергетической оценки многовариантных пастбищных систем со злаковыми травостоями, созданными в 1946 году. Даны количественные показатели по сбору обменной энергии, совокупным затратам на её производство, окупаемости затрат в зависимости от системы ведения пастбищ. Изучена эффективность совокупных затрат в виде овеществлённого труда (на семена, удобрения, сельскохозяйственные машины, средства огораживания загонов и прочее) и живого труда (работы трактористов, пастухов и строителей и др.). Обоснована высокая агроэнергетическая эффективность изучаемых пастбищных систем благодаря мобилизации в продукционный процесс природных факторов, долевое участие которых в структуре производства обменной энергии составило 69–84%. Природные факторы, участвующие в продукционном процессе луговых агроэкосистем, характеризуются большим разнообразием. Это не только использование солнечной энергии и азотфиксация бобовыми травами, но и долголетие травостоев, самовозобновление фитоценозов, дерновообразовательный процесс (повышение плодородия почвы), получение дешёвого корма и улучшение здоровья животных при летнем выпасе. Роль возобновляемых природных факторов выявлена на основе балансового метода, принятого в экономике (по разнице сбора обменной энергии и антропогенных затрат). Благодаря ведущей роли природных факторов в структуре произведённой продукции агроэнергетический коэффициент окупаемости совокупных затрат антропогенной энергии (АК) за счёт сбора обменной энергии достигал 3–6 раз в среднем за 45 лет. Разработанные в результате долголетних исследований многовариантные энергосберегающие пастбищные системы обосновывают возможность рекомендовать их производству с учётом применения различного уровня энергозатрат. Ключевые слова: культурные пастбища, системы ведения, долголетние травостои, сбор обменной энергии, совокупные антропогенные затраты, окупаемость затрат. The investigation was conducted at the Federal Williams Research Center of Fodder Production and Agroecology and was aimed at testing energy efficiency of gramineous and legume-gramineous swards. This article presents the results obtained on pasture ecosystems with gramineous planted in 1946. Exchange energy yield, total production costs and economic effectiveness were analyzed. Total production costs comprised costs for seeds, fertilizers, machinery, construction materials, labor, etc. Introduction of natural factors into the production process resulted in higher energy efficiency. Their share amounted to 69–84% in the final exchange energy yield. There are a lot of natural factors that affect grass productivity such as solar energy, nitrogen-fixation, sward longevity and regeneration, soil fertility, low-cost feed production, and livestock health. The value of natural factors was determined according to the balance method (by the difference between exchange energy yield and anthropogenic costs). Since environmental factors had a leading role in the production process, the return rate raised by 3–6 times for 45 years due to exchange energy increase. Therefore, pasture ecosystems developed can be recommended for a large-scale forage production.


2008 ◽  
Vol 68 (4) ◽  
pp. 875-883 ◽  
Author(s):  
LH. Sipaúba-Tavares ◽  
AML. Pereira

Large-scale lab culture of Ankistrodesmus gracilis and Diaphanososma birgei were evaluated by studying the biology and biochemical composition of the species and production costs. Ankistrodesmus gracilis presented exponential growth until the 6th day, with approximately 144 x 10(4) cells.mL-1, followed by a sharp decrease to 90 x 10(4) cells.mL-1 (8th day). Algae cells tended to increase again from the 11th day and reached a maximum of 135 x 10(4) cells.mL-1 on the 17th day. D. birgei culture showed exponential growth until the 9th day with 140 x 10² individuals.L-1, and increased again as from the 12th day. Algae A. gracilis and zooplankton D. birgei contain 47 to 70% dry weight protein and over 5% dry weight carbohydrates. The most expensive items in the context of variable costs were labor and electricity. Data suggested that temperature, nutrients, light availability and culture management were determining factors on productivity. Results indicate that NPK (20-5-20) may be used directly as a good alternative for mass cultivation when low costs are taken into account, promoting adequate growth and nutritional value for cultured A. gracilis and D. birgei.


Author(s):  
Keiya Ishiyama ◽  
Ryo Koike ◽  
Yasuhiro Kakinuma ◽  
Tetsuya Suzuki ◽  
Takanori Mori

Additive manufacturing (AM) for metals has attracted attention from industry because of its great potential to enhance production efficiency and reduce production costs. Directed energy deposition (DED) is a metal AM process suitable to produce large-scale freeform metal products. DED entails irradiating the baseplate with a laser beam and launching the metal powder onto the molten spot to produce a metal part on the baseplate. Because the process enables powder from different materials to be used, DED is widely applicable to valuable production work such as for a dissimilar material joint, a graded material, or a part with a special structure. With regard to parts with a special structure, directional solidification can prospectively be used in the power plant and aerospace industries because it can enhance the stiffness in a specific direction via only a simple process. However, conventional approaches for directional solidification require a special mold in order to realize a long-lasting thermal gradient in the part. On the other hand, from the viewpoint of thermal distribution in a produced part, DED is able to control the gradient by controlling the position of the molten pool, i.e., the position of the laser spot. Moreover, unlike casting, the thermal gradient can be precisely oriented in the expected direction, because the laser supplies heat energy on the regulated spot. In this study, the applicability of DED to directional solidification in Inconel® 625 is theoretically and experimentally evaluated through metal structure observation and Vickers hardness measurements. Furthermore, the effect of two different cooling processes on directional solidification is also considered with the aim of improving the mechanical stiffness of a part produced by DED. The observations and experimental results show that both the cooling methods (baseplate cooling and intermittent treatment with coolant) are able to enhance the hardness while retaining the anisotropy.


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