1. Mechanism of action, potency and efficacy : considerations for cell therapiesCarl G. Simon Jr., Erich H. Bozenhardt, Christina M. Celluzzi, David Dobnik, Melanie L. Grant, Uma Lakshmipathy, Thiana Nebel, 2024, original scientific article Abstract: One of the most challenging aspects of developing advanced cell therapy products (CTPs) is defining the mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented that is consistent with the existing regulatory guidelines, but also accommodates what has been learned from the 27 US FDA-approved CTPs. Available information regarding MOA, potency and efficacy for the 27 FDA-approved CTPs is reviewed to provide background and perspective. Potency process and efficacy process charts are introduced to clarify and illustrate the relationships between six key concepts: MOA, potency, potency test, efficacy, efficacy endpoint and efficacy endpoint test. Careful consideration of the meaning of these terms makes it easier to discuss the challenges of correlating potency test results with clinical outcomes and to understand how the relationships between the concepts can be misunderstood during development and clinical trials. Examples of how a product can be “potent but not efficacious” or “not potent but efficacious” are presented. Two example applications of the framework compare how MOA is assessed in cell cultures, animal models and human clinical trials and reveals the challenge of establishing MOA in humans. Lastly, important considerations for the development of potency tests for a CTP are discussed. These perspectives can help product developers set appropriate expectations for understanding a product’s MOA and potency, avoid unrealistic assumptions and improve communication among team members during the development of CTPs.
Keywords: cell therapy product, efficacy endpoint test, mechanism of action, potency test, metrology
Published in DiRROS: 27.05.2024; Views: 36; Downloads: 22
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2. The role of relative humidity on crystallization of calcium carbonate from calcium acetoacetate precursorAndreja Pondelak, Francesca Rosi, Celeste Maurich, Costanza Miliani, Srečo D. Škapin, Andrijana Sever Škapin, 2019, original scientific article Abstract: Calcium acetoacetate, Ca(OAcAc)2, was exposed 7, 30 and 365 days to different values of relative humidity (33%, 48%, 75% and 96%) at 40 °C in order to study its transformation to CaCO3. The resulting Ca(OAcAc)2 decomposition and the time dependence of the phase transformations were monitored and critically evaluated by Fourier transform infrared spectroscopy, field emission scanning electron microscopy and X-ray powder diffraction. The impact of relative humidity on CaCO3 polymorph formation was thoroughly assessed. In all of the conditions used and for all ageing periods, the formed crystal structure is found to be vaterite. At the lowest relative humidity (33%), the amorphous CaCO3 remains more or less almost untransformed even after one year of exposure. It is proposed that the reason for the stability of amorphous CaCO3 is due to the limited amount of physisorbed water on the surfaces of the particles, which is considered the driving force for its transformation. However, the carbonation process is faster in the case of the highest humidity (96%). The findings are not only important for better solutions in the field of cultural heritage, but also shed new light on the fundamental mechanism of CaCO3 crystallization.
Keywords: calcium acetoacetate, relative humidity, carbonation, amorphous carbonate, vaterite, mechanism
Published in DiRROS: 22.11.2023; Views: 409; Downloads: 166
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3. Catalytic lignin valorisation by depolymerisation, hydrogenation, demethylation and hydrodeoxygenation : mechanism, chemical reaction kinetics and transport phenomenaTina Ročnik, Blaž Likozar, Edita Jasiukaityte, Miha Grilc, 2022, review article Keywords: lignin, valorisation, depolymerisation, mechanism, kinetic modelling, transport phenomena
Published in DiRROS: 01.07.2022; Views: 589; Downloads: 412
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6. Photocatalytic, electrocatalytic and photoelectrocatalytic degradation of pharmaceuticals in aqueous media : analytical methods, mechanisms, simulations, catalysts and reactorsBelisa Alcantara Marinho, Luka Suhadolnik, Blaž Likozar, Matej Huš, Živa Marinko, Miran Čeh, 2022, review article Keywords: advanced oxidation process, persistent organic compounds, pharmaceutical by- products, degradation mechanism, reactor design, analytical methods
Published in DiRROS: 10.03.2022; Views: 693; Downloads: 540
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7. Catalytic hydrocracking reactions of tetralin biomass tar model compound to benzene, toluene and xylenes (BTX) over metal-modified ZSM-5 in ambient pressure reactorAndrii Kostyniuk, David Bajec, Blaž Likozar, 2022, original scientific article Keywords: catalytic hydrocracking reactions, ring opening mechanism, model biomass tar, benzene/toluene/xylenes (BTX), metal-doped HZSM-5 zeolite material, deposited coke deactivation
Published in DiRROS: 10.03.2022; Views: 703; Downloads: 544
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8. Mechanisms of copper-based catalyst deactivation during CO [sub] 2 reduction to methanolAnže Prašnikar, Andraž Pavlišič, Francisco Ruiz-Zepeda, Janez Kovač, Blaž Likozar, 2019, original scientific article Keywords: catalyst deactivation, methanol synthesis, deactivation mechanism, modelling
Published in DiRROS: 24.11.2020; Views: 1349; Downloads: 985
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9. A review of methane activation reactions by halogenation : catalysis, mechanism, kinetics, modeling, and reactorsDavid Bajec, Matic Grom, Damjan Lašič Jurković, Andrii Kostyniuk, Matej Huš, Miha Grilc, Blaž Likozar, Andrej Pohar, 2020, review article Keywords: methane, halogenation, catalysis, density functional theory, kinetics, mechanism
Published in DiRROS: 16.04.2020; Views: 2143; Downloads: 1360
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10. Postulates for validating TLR4 agonistsMateja Manček Keber, Roman Jerala, 2015, review article Abstract: TLRs play a central role in the innate immune response, recognizing a variety of molecular
structures characteristic of pathogens. Although TLR4, together with its co-receptor
myeloid differentiation-2 (MD-2), recognize bacterial LPS and therefore Gram-negative
bacterial infections, it also plays a key role in many other pathophysiological processes,
including sterile inflammation and viral infection. Specifically, numerous endogenous
agonists of TLR4 of notably diverse nature, ranging from proteins to metal ions, have
been reported. Direct activation of a single receptor by such a range of molecular signals
is very difficult to explain from a structural and mechanistic point of view. It is likely
that only a subset of these directly activate the TLR4–MD-2 complex. We propose three
postulates aimed at distinguishing the direct agonists of TLR4 from indirect activators.
These postulates are as follows: (i) that the agonist requires the TLR4/MD-2 receptor complex;
(ii) that agonist formed synthetically or in situ must activate the receptor complex
in order to eliminate artifacts of contamination by other agonists; and (iii) that a specific
molecular interaction between the agonist and TLR4/MD-2 must be identified. The same
type of postulates can be applied to pattern recognition receptors in general.
Keywords: TLR4 agonists, molecular mechanism, ligand recognition
Published in DiRROS: 26.01.2015; Views: 4983; Downloads: 474
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