Commercialization of cellular immunotherapies for cancer

2016 ◽  
Vol 44 (2) ◽  
pp. 329-332 ◽  
Author(s):  
Anthony Walker ◽  
Robert Johnson
Keyword(s):  
Economies Of Scale ◽  
Technology Development ◽  
Standard Of Care ◽  
Production Costs ◽  
Capital Investments ◽  
Cell Therapies ◽  
Antibody Therapeutics ◽  
Commercial Viability ◽  
A Cell ◽  
Very High

Successful commercialization of a cell therapy requires more than proving safety and efficacy to the regulators. The inherent complexity of cellular products delivers particular manufacturing, logistical and reimbursement hurdles that threaten commercial viability for any therapy with a less than spectacular clinical profile that truly changes the standard of care. This is particularly acute for autologous cell therapies where patients receive bespoke treatments manufactured from a sample of their own cells and where economies of scale, which play an important role in containing the production costs for small molecule and antibody therapeutics, are highly limited. Nevertheless, the promise of ‘game-changing’ efficacy, as exemplified by very high levels of complete responses in refractory haematological malignancies, has attracted capital investments on a vast scale, and the attendant pace of technology development provides promising indicators for future clinical and commercial success.

scholarly journals The evolution of alternative splicing in glioblastoma under therapy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lin Wang ◽  
Karin Shamardani ◽  
Husam Babikir ◽  
Francisca Catalan ◽  
Takahide Nejo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Standard Of Care ◽  
Surface Proteins ◽  
Adult Brain ◽  
Primary Tumors ◽  
Cell Therapies ◽  
Therapeutic Development ◽  
Human Gbm ◽  
Tissue Specimens ◽  
Splicing Patterns

Abstract Background Alternative splicing is a rich source of tumor-specific neoantigen targets for immunotherapy. This holds promise for glioblastomas (GBMs), the most common primary tumors of the adult brain, which are resistant to standard-of-care therapy. Although most clinical trials enroll patients at recurrence, most preclinical studies have been done with specimens from primary disease. There are limited expression data from GBMs at recurrence and surprisingly little is known about the evolution of splicing patterns under therapy. Result We profile 37 primary-recurrent paired human GBM specimens via RNA sequencing. We describe the landscape of alternative splicing in GBM at recurrence and contrast that to primary and non-malignant brain-tissue specimens. By screening single-cell atlases, we identify cell-type-specific splicing patterns and novel splicing events in cell-surface proteins that are suitable targets for engineered T cell therapies. We identify recurrent-specific isoforms of mitogen-activated kinase pathway genes that enhance invasiveness and are preferentially expressed by stem-like cells. Conclusion These studies shed light on gene expression in recurrent GBM and identify novel targets for therapeutic development.

scholarly journals Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Michael Stumpp
Keyword(s):  
Single Agent ◽  
Standard Of Care ◽  
Cooperative Binding ◽  
Wild Type ◽  
Inhibitory Potency ◽  
Alpha Variant ◽  
The Individual ◽  
Very High ◽  
Comprehensive Study

Abstract SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron, as of December 2021. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

Cloud-TM

2015 ◽  
pp. 749-781
Author(s):  
João Barreto ◽  
Pierangelo Di Sanzo ◽  
Roberto Palmieri ◽  
Paolo Romano
Keyword(s):  
Cloud Computing ◽  
Large Scale ◽  
Economies Of Scale ◽  
Service Providers ◽  
Cloud Service ◽  
Capital Investments ◽  
Barriers To Entry ◽  
Capital Costs ◽  
Programming Paradigms ◽  
Pricing Schemes

By shifting data and computation away from local servers towards very large scale, world-wide spread data centers, Cloud Computing promises very compelling benefits for both cloud consumers and cloud service providers: freeing corporations from large IT capital investments via usage-based pricing schemes, drastically lowering barriers to entry and capital costs; leveraging the economies of scale for both services providers and users of the cloud; facilitating deployment of services; attaining unprecedented scalability levels. However, the promise of infinite scalability catalyzing much of the recent hype about Cloud Computing is still menaced by one major pitfall: the lack of programming paradigms and abstractions capable of bringing the power of parallel programming into the hands of ordinary programmers. This chapter describes Cloud-TM, a self-optimizing middleware platform aimed at simplifying the development and administration of applications deployed on large scale Cloud Computing infrastructures.

scholarly journals Overcoming the Challenges for a Mass Manufacturing Machine for the Assembly of PEMFC Stacks

Machines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 66 ◽  
Author(s):  
Porstmann ◽  
Wannemacher ◽  
Richter
Keyword(s):  
Fuel Cell ◽  
Economies Of Scale ◽  
Polymer Electrolyte Membrane ◽  
Cell System ◽  
Active Components ◽  
Fuel Cell Stack ◽  
Electrolyte Membrane ◽  
Modular Concept ◽  
A Cell ◽  
Manufacturing Machine

One of the major obstacles standing in the way of a break-through in fuel cell technology is its relatively high costs compared to well established fossil-based technologies. The reasons for these high costs predominantly lie in the use of non-standardized components, complex system components, and non-automated production of fuel cells. This problem can be identified at multiple levels, for example, the electrochemically active components of the fuel cell stack, peripheral components of the fuel cell system, and eventually on the level of stack and system assembly. This article focused on the industrialization of polymer electrolyte membrane fuel cell (PEMFC) stack components and assembly. To achieve this, the first step is the formulation of the requirement specifications for the automated PEMFC stack production. The developed mass manufacturing machine (MMM) enables a reduction of the assembly time of a cell fuel cell stack to 15 minutes. Furthermore the targeted automation level is theoretically capable of producing up to 10,000 fuel cell stacks per year. This will result in a ~50% stack cost reduction through economies of scale and increased automation. The modular concept is scalable to meet increasing future demand which is essential for the market ramp-up and success of this technology.

scholarly journals Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

2020 ◽  
Vol 7 (3) ◽  
pp. 112 ◽  
Author(s):  
Vanessa Allwardt ◽  
Alexander J. Ainscough ◽  
Priyalakshmi Viswanathan ◽  
Stacy D. Sherrod ◽  
John A. McLean ◽  
...  
Keyword(s):  
Technology Development ◽  
Technology Readiness ◽  
Disruptive Technology ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Commercial Viability ◽  
Performance Benchmarks ◽  
Using Data ◽  
Further Development

Organs-on-a-Chip (OOAC) is a disruptive technology with widely recognized potential to change the efficiency, effectiveness, and costs of the drug discovery process; to advance insights into human biology; to enable clinical research where human trials are not feasible. However, further development is needed for the successful adoption and acceptance of this technology. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. In this review, we reported on the consensus around existing challenges and necessary performance benchmarks that are required toward the broader adoption of OOACs in the next five years, and we defined a potential roadmap for future translational development of OOAC technology. We provided a clear snapshot of the current developmental stage of OOAC commercialization, including existing platforms, ancillary technologies, and tools required for the use of OOAC devices, and analyze their technology readiness levels. Using data gathered from OOAC developers and end-users, we identified prevalent challenges faced by the community, strategic trends and requirements driving OOAC technology development, and existing technological bottlenecks that could be outsourced or leveraged by active collaborations with academia.

Thermally Regenerative Hydrogen/Oxygen Fuel Cell Power Cycles

1988 ◽  
Vol 110 (2) ◽  
pp. 107-112 ◽  
Author(s):  
J. H. Morehouse
Keyword(s):  
High Temperature ◽  
Fuel Cell ◽  
Energy Production ◽  
Technology Development ◽  
Thermal Dissociation ◽  
Electrical Energy ◽  
Power Cycles ◽  
Electrical Energy Production ◽  
Oxygen Fuel ◽  
Very High

Two thermodynamic power cycles are analytically examined for future engineering feasibility. These power cycles use a hydrogen-oxygen fuel cell for electrical energy production and use the thermal dissociation of water for regeneration of the hydrogen and oxygen. The first cycle uses a thermal energy input at over 2000K to thermally dissociate the water. The second cycle dissociates the water using an electrolyzer operating at high temperature (1300K) which receives both thermal and electrical energy as inputs. The results show that while the processes and devices of the 2000K thermal system exceed current technology limits, the high temperature electrolyzer system appears to be a state-of-the-art technology development, with the requirements for very high electrolyzer and fuel cell efficiencies seen as determining the feasibility of this system.

A Techno-Economic Optimization of the Power Conversion System of a Very High Temperature Reactor

2006 ◽  
Author(s):  
Christine Mansilla ◽  
Michel Dumas ◽  
Franc¸ois Werkoff
Keyword(s):  
High Temperature ◽  
Power Conversion ◽  
Minimum Cost ◽  
Production Costs ◽  
Total Production ◽  
Economic Optimization ◽  
Very High Temperature Reactor ◽  
Conversion System ◽  
High Temperature Reactor ◽  
Very High

Generation IV nuclear reactors will not be implemented unless they enable lower production costs than with the current systems. In such a context a techno-economic optimization method was developed and then applied to the power conversion system of a very high temperature reactor. Techno-economic optimization consists in minimizing an objective function that depends on technical variables and economic ones. The advantage of the techno-economic optimization is that it can take into account both investment costs and operating costs. A techno-economic model was implemented in a specific optimization software named Vizir, which is based on genetic algorithms. The calculation of the thermodynamic cycle is performed by a software named Tugaz. The results are the values of the decision variables that lead to a minimum cost, according to the model. The total production cost is evaluated. The influence of the various variables and constraints is also pointed out.

scholarly journals Global prospects of unconventional oil in the turbulent market: a long term outlook to 2040

2018 ◽  
Vol 73 ◽  
pp. 67 ◽  
Author(s):  
Nikita O. Kapustin ◽  
Dmitry A. Grushevenko
Keyword(s):  
Large Scale ◽  
Technology Development ◽  
Business Environment ◽  
Production Costs ◽  
Liquid Fuels ◽  
Open Pit ◽  
Open Pit Mining ◽  
Resource Base ◽  
Unconventional Oil ◽  
The Usa

Unconventional oils have taken the global oil industry by storm and have secured an 8% share in the global liquid fuels production in under 20 years. And it is without a doubt that these resources will continue to play an important role in the future. Cost analysis of unconventional oil types has shown that Light Tight Oil (LTO) or shale oil still holds potential for technological and economical improvement, however, the revolutionary stage in development has probably already been passed in the US. For the rest of the world, the issue of kick starting LTO production lies as much in the fields of adapting the existing technologies, as overcoming economic, legislative and environmental barriers. The same cannot be said for heavy oil and bitumen production, as open pit mining is demonstrating cost escalation and resource base depletion, whilein situproduction approach has reached the limit of technological progress and production costs are mostly determined by external factors. Oil price fluctuation and the emergence of more economically viable unconventional oil sources have shifted attention away from kerogen oil and substantially halted production technologies development. The forecast of unconventional oil was conducted along two scenarios: Baseline (a business-as-usual scenario) and Technological (scenario of forced technology development and transfer). The share of unconventional oil in global crude production will increase to 17–21%, depending on scenario. The main difference between scenarios is the rate of kerogen production, which benefits from the favorable conditions of the Technological scenario. Large-scale LTO production will remain a local North American phenomenon in both scenarios. More important than geological or technological factors is the unique business environment, characteristic for the USA, which would be impossible to replicate in any other country. Expansion of unconventional oil production as stimulated competition on the liquid fuels market. Conventional oil producers have mostly adapted to the new environment and will continue to dominate in the forecast period. The greatest pressure is put on the more costly alternative supply sources: biofuels, coal-to-liquid and gas-to-liquid; which have the least promising prospects in the current market.

Design and Technology Development Status and Design Considerations for Innovative Small and Medium Sized Reactors 1

2009 ◽  
Vol 131 (6) ◽  
Author(s):  
Vladimir Kuznetsov
Keyword(s):  
Nuclear Power ◽  
Economies Of Scale ◽  
Technology Development ◽  
Design And Technology ◽  
International Programs ◽  
Power Station ◽  
Plant Construction ◽  
Electrical Grids ◽  
Incremental Capacity ◽  
Maintenance Requirements

There is continuing interest in Member States in the development and application of small and medium sized reactors (SMRs), i.e., the reactors with an equivalent electric power of less than 700 MW. In 2006–2007, several distinct “families” of innovative SMRs comprising more than 50 innovative concepts and designs have been analyzed or developed by national or international programs involving Argentina, Brazil, China, Croatia, France, India, Indonesia, Italy, Japan, Republic of Korea, Lithuania, Morocco, Russian Federation, South Africa, Turkey, USA, and Vietnam. Innovative SMRs are under development for all principal reactor lines. The target dates when they could be ready for deployment protrude from 2010 to 2030. The designers of innovative small and medium sized reactors pursue new design and deployment strategies making use of certain advantages provided by smaller reactor size and capacity to achieve reduced design complexity and simplified operation and maintenance requirements and to provide for incremental capacity increase through multiple plant clustering or multimodule plant construction. Competitiveness of SMRs depends on the incorporated strategies to overcome loss of economies of scale but equally it depends on finding appropriate market niches for such reactors, which generically include markets with limited investment capability potentially benefiting from reaching the targeted nuclear power station capacity incrementally, small electrical grids, off-grid locations, and nonelectrical applications of nuclear power.

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