Kinetic and Compositional Study of Phenolic Extraction from Olive Leaves (var.Serrana) by Using Power Ultrasound

[EN] Power ultrasound is being used as a novel technique for process intensification. In this study, the feasibility of using power ultrasound to improve the phenolic extraction from olive leaves was approached taking both compositional and kinetic issues into account and also determining the influence of the main process parameters (the electric power supplied, emitter surface and temperature). For this purpose, the extraction kinetics were monitored by measuring the total phenolic content and antioxidant capacity and mathematically described by Naik's model, and HPLC DAD/MS MS was used to identify and quantify the main polyphenols. The electric power supplied and the emitter surface greatly affected the effective ultrasonic power applied to the medium, and hence the extraction rate. However, the influence of temperature on ultrasound assisted extraction was not clear. Compared with conventional extraction, ultrasound assisted extraction reduced the extraction time from 24 h to 15 min and did not modify the extract composition. Industrial relevance: Olive crop produces a significant quantity of byproducts (leaves, branches, solid and liquid wastes), coming from the tree pruning, fruit harvest and oil production, which are rich in phenolic compounds with bioactive properties. The extraction of the bioactive compounds could be an interesting option with which to increase the value of these byproducts, as it requires efficient extraction techniques in order to reduce processing costs and improve productivity. In this sense, ultrasound assisted extraction is considered a novel technique used as ameans of intensifying a slow process, such as the leaching of polyphenols fromvegetablematrices. In order to further address the industrial applications of ultrasound assisted extraction, a kinetic study should be carried out determining both the effective energy introduced into the medium, as well as its influence on the extract quality.The authors thank the Generalitat Valenciana (PROMETEO/2010/062 and PROMETEO/2012/007) for its financial support. M. H. Ahmad Qasem was the recipient of a fellowship from Ministerio de Educacion, Cultura y Deporte of Spain (Programa de Formacion de Profesorado Universitario del Programa Nacional de Formacion de Recursos Humanos de Investigacion).Ahmad-Qasem Mateo, MH.; Canovas, J.; Barrajon-Catalan, E.; Micol, V.; Cárcel Carrión, JA.; García Pérez, JV. (2013). Kinetic and Compositional Study of Phenolic Extraction from Olive Leaves (var.Serrana) by Using Power Ultrasound. Innovative Food Science and Emerging Technologies. (17):120-129. https://doi.org/10.1016/j.ifset.2012.11.008S1201291

Development of a Novel Anti-CD19 Chimeric Antigen Receptor : A Paradigm for an Affordable CAR T Cell Production at Academic Institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdc Il2rd/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients

Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdcscid Il2rdtm1Wjl/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients

Quality by Design: Development of Safe and Efficacious Full-Thickness Acellular Dermal Matrix Based on EuroGTPII Methodologies

Acellular dermis; Risk assessment; SafetyDermis acel·lular; Avaluació de riscos; SeguretatDermis acelular; Evaluación de riesgos; SeguridadBackground: The activities of tissue establishments are constantly and rapidly evolving. The development of a new type of allograft, full-thickness acellular dermal matrix, with high mechanical properties to be used in tendon repair surgeries and abdominal wall reconstruction, has determined the need for quality by design process in order to assess evidence of quality, safety and efficacy. The EuroGTPII methodologies were specifically tailored to perform the risk assessment, identify and suggest tests in order to mitigate the potential risk consequences of a novel tissue preparation implementation. Methods: The new allograft and associated preparation processes were assessed using the EuroGTP methodologies and characterized to properly evaluate the novelty (Step 1), identify and quantify the potential risks and risk consequences (Step 2), and define the extent of pre-clinical and clinical assessments required to mitigate the risks identified in the assessment (Step 3). Results: Four risk consequences associated with the preparation process were identified: (i) implant failure related with tissue procurement and the reagents used during the decellularization protocol; (ii) unwanted immunogenicity related with the processing; (iii) disease transmission linked with the processing, reagents used, reduction in the reliability of microbiology testing and the storage conditions; and (iv) toxicity related to the reagents used and handling of the tissue during clinical application. The outcome of the risk assessment was a low level of risk. Nevertheless, it determined the need for a series of risk mitigation strategies proposed to reduce each individual risk and to provide additional evidence of the safety and efficacy of full-thickness acellular dermal matrix grafts. Conclusion: EuroGTPII methodologies allow us to identify the risks and ensure the correct definition of pre-clinical assessments required to address and mitigate the potential risk consequences, before proceeding with clinical use of the new allografts in patients.This work was supported by the European Union’s Health Programme (2014–2020), Grant Agreement number: 709567 – EuroGTP II – HP-PJ-2015. This study represents the views of the authors only and is their sole responsibility; it cannot be considered to reflect the views of the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains

EuroGTP II : a tool to assess risk, safety and efficacy of substances of human origin

A systematic methodology, able to assess risk and predict clinical safety and efficacy of Substances of Human Origin' (SoHO) has been developed. The model consists of a risk based approach taking into account factors such as novelty of the product, preparation process, clinical indication, and its technical complexity

EuroGTPII: a tool to assess risk, safety and efficacy of substances of human origin

A systematic methodology, able to assess risk and predict clinical safety and efficacy of Substances of Human Origin\u2019 (SoHO) has been developed. The model consists of a risk based approach taking into account factors such as novelty of the product, preparation process, clinical indication, and its technical complexity

Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdcscid Il2rdtm1Wjl/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients