scholarly journals Transgenic goats producing an improved version of cetuximab in milk

2020 ◽  
Author(s):  
Götz Laible ◽  
Sally Cole ◽  
Brigid Brophy ◽  
Paul Maclean ◽  
Li How Chen ◽  
...  

ABSTRACTTherapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were selected for detailed characterization. Both showed stable genotypes and cetuximab production levels of up to 10g/L. The mAb could be readily purified and showed improved characteristics compared to Erbitux. The goat-produced cetuximab (gCetuximab) lacked a highly immunogenic epitope that is part of Erbitux. Moreover, it showed enhanced binding to CD16 and increased antibody-dependent cell-dependent cytotoxicity compared to Erbitux. This indicates that these goats produce an improved cetuximab version with the potential for enhanced effectiveness and better safety profile compared to treatments with Erbitux. In addition, our study validates transgenic goats as an excellent platform for large-scale production of therapeutic mAbs.

1988 ◽  
Vol 6 (5) ◽  
pp. 518-523 ◽  
Author(s):  
Malcolm Rhodes ◽  
John Birch

2013 ◽  
Vol 2013 (DPC) ◽  
pp. 000377-000397
Author(s):  
Jon G. Aday ◽  
Ted Tessier ◽  
Kazuhisa Itoi ◽  
Satoshi Okude

Embedded die substrate technologies are being developed in an assortment of configurations and for different market segments. The technology being discussed in this paper will be focused on both a fan out technology – ChipsetT Fan-Out and a system in package approach (ChipsetT SiP) in which a multiple component bill of materials (BOM) is used. The Chipset process is based on the WABE (Wafer and Board Level Embedding) technology. WABE technology is based on co-lamination of multilayer polyimide flex wiring and conductive z-axis sintered metal interconnections. This ChipsetT Fan Out technology allows for large scale production of fan out type solutions which can allow for very thin packages in addition to unique pin out solutions such as pin compatibility for a competitor part. The ChipsetT SiP also allows embedding of single or multiple silicon die and/or components. Additional components can also be placed using conventional SMT on the top or bottom side of the package. There is a great deal of design flexibility with this technology which makes it a great solution for applications trying to reduce their x-y size or z-height. When utilizing RDL technology on the embedded die we are able to do the fine pitch routing in order to allow the substrate to route at larger pitches ensuring an overall cost effective solution. This paper will focus on the different classes of applications that have benefited from this technology and will discuss the benefits and tradeoffs of the different solutions that have been engineered. Assembly and reliability data will be presented on several of the applications showing a robust solution set.


2019 ◽  
Vol 20 (23) ◽  
pp. 5862 ◽  
Author(s):  
Daniel Brady ◽  
Alessandro Grapputo ◽  
Ottavia Romoli ◽  
Federica Sandrelli

The alarming escalation of infectious diseases resistant to conventional antibiotics requires urgent global actions, including the development of new therapeutics. Antimicrobial peptides (AMPs) represent potential alternatives in the treatment of multi-drug resistant (MDR) infections. Here, we focus on Cecropins (Cecs), a group of naturally occurring AMPs in insects, and on synthetic Cec-analogs. We describe their action mechanisms and antimicrobial activity against MDR bacteria and other pathogens. We report several data suggesting that Cec and Cec-analog peptides are promising antibacterial therapeutic candidates, including their low toxicity against mammalian cells, and anti-inflammatory activity. We highlight limitations linked to the use of peptides as therapeutics and discuss methods overcoming these constraints, particularly regarding the introduction of nanotechnologies. New formulations based on natural Cecs would allow the development of drugs active against Gram-negative bacteria, and those based on Cec-analogs would give rise to therapeutics effective against both Gram-positive and Gram-negative pathogens. Cecs and Cec-analogs might be also employed to coat biomaterials for medical devices as an approach to prevent biomaterial-associated infections. The cost of large-scale production is discussed in comparison with the economic and social burden resulting from the progressive diffusion of MDR infectious diseases.


2019 ◽  
Vol 21 (2) ◽  
pp. 198-204 ◽  
Author(s):  
Kaiyu Xie ◽  
Ali Reza Kamali

Molten salt electrolytic reduction of Fe2O3 in the presence of water is proposed as a sustainable and cost-effective approach for large-scale production of iron.


2007 ◽  
Vol 534-536 ◽  
pp. 773-776
Author(s):  
R. Cook ◽  
I.T.H. Chang ◽  
C. Lucien Falticeanu

P/M aluminium components are attracting interest in an increasing variety of industries due to the possibilities for weight saving in engineering parts. There are many processes for manufacturing from powder feedstocks that are either in production, becoming commercialised or still undergoing development. The nature of these processes and the required properties of the end products mean that powders of different particle size, shape, composition and microstructure must be produced. The requirements of various processes requiring aluminium and aluminium alloy powders for metal matrix composites, laser sintering, powder forging and metal injection moulding are discussed in relation to powder particle size and structure. The key requirement of the powder manufacturer is to supply cost effective materials for these different processes. This may require compromises to be made by the supplier and consumer while the techniques evolve from development to large scale production.


1994 ◽  
Vol 37 (2) ◽  
pp. 179-184 ◽  
Author(s):  
Sari Ala-Uotila ◽  
Anne Marjamäki ◽  
Marja-Terttu Matikainen ◽  
Markku Jalkanen

Catalysts ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 60
Author(s):  
Muhammad Amtiaz Nadeem ◽  
Mohd Adnan Khan ◽  
Ahmed Abdeslam Ziani ◽  
Hicham Idriss

The conversion of solar to chemical energy is one of the central processes considered in the emerging renewable energy economy. Hydrogen production from water splitting over particulate semiconductor catalysts has often been proposed as a simple and a cost-effective method for large-scale production. In this review, we summarize the basic concepts of the overall water splitting (in the absence of sacrificial agents) using particulate photocatalysts, with a focus on their synthetic methods and the role of the so-called “co-catalysts”. Then, a focus is then given on improving light absorption in which the Z-scheme concept and the overall system efficiency are discussed. A section on reactor design and cost of the overall technology is given, where the possibility of the different technologies to be deployed at a commercial scale and the considerable challenges ahead are discussed. To date, the highest reported efficiency of any of these systems is at least one order of magnitude lower than that deserving consideration for practical applications.


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