Corn starch was oxidised using sodium hypochlorite to enhance its film forming property and reduce viscosity. This oxidised starch (OS) was further modified by n-octenyl succinic anhydride (OSA) to ...introduce hydrophobicity. This dual modified starch (OS-OSA) was characterized for crystalline and thermal attributes. The emulsion stability, viscosity and particle size of OS-OSA based emulsion with 60% soybean oil loading was compared with OS and gum Arabic (GA). The spray dried microcapsules using OS-OSA and GA as wall materials at 20% (w/v) containing emulsions demonstrated similar surface morphology (smooth surface devoid of cracks) and particle size. Microencapsulation with OS showed lower encapsulation efficiency (13%) than those with OS-OSA and GA (similar at 58%). The half-life of OS-OSA (39 weeks) microcapsules was lower than GA (44 weeks) but the final encapsulation efficiency after 18 weeks was similar in both cases. Thus OS-OSA corn starch can potentially replace gum Arabic for microencapsulation applications.
•Corn starch was oxidised using NaOCl to alter viscosity and film forming property.•This oxidised starch was esterified using octenyl succinic anhydride.•This dual modified starch was characterized for its structure and functionality.•The emulsifying & microencapsulation property of dual modified starch were studied.•This starch demonstrated to be a potential substitute for gum Arabic.
On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen ...receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.
Ginger oleoresin was emulsified with gum acacia and encapsulated in a sucrose matrix by co-crystallization. The increased void space and surface area of sucrose provided a porous base for the ...incorporation of oleoresin. This co-crystallization led to modification from crystalline to irregular agglomerates, as evident from X-ray diffraction and differential scanning calorimetry. Hygroscopicity, water sorption isotherms and water activity demonstrated changes due to the change in crystallinity of sucrose. The active components such as 6-, 8- and 10-gingerols and 6-shogaol were quantified by HPLC. The encapsulation efficiency of 6-gingerol was 45.59%. The storage kinetics at different relative humidity levels and temperatures indicated 6-gingerol to be the most stable among the gingerols studied. A temperature of 25 °C and relative humidity of 33% proved to be the best storage conditions for the ginger flavoured sugar cubes. Thus, co-crystallization for the encapsulation of ginger oleoresin serves a dual purpose,
i.e.
, protection and a mode of delivering a spicy flavour.
Ginger oleoresin was emulsified with gum acacia and encapsulated in a sucrose matrix by co-crystallization for its protection and as a mode of flavour delivery. Physical characterization and storage studies under different conditions were performed.
Chimeric antigen receptor (CAR) T-cells have demonstrated significant efficacy in targeting hematological malignancies, and their use continues to expand. Despite substantial efforts spent on the ...optimization of protocols for CAR T-cell manufacturing, critical parameters of cell culture such as pH or oxygenation are rarely actively monitored during cGMP CAR T-cell generation. A comprehensive understanding of the role that these factors play in manufacturing may help in optimizing patient-specific CAR T-cell therapy with maximum benefits and minimal toxicity.
This retrospective study examined cell culture supernatants from the manufacture of CAR T-cells for 20 patients with B-cell malignancies enrolled in a phase 1/2 clinical trial of anti-CD22 CAR T-cells. MetaFLEX was used to measure supernatant pH, oxygenation, and metabolites, and a Bio-Plex assay was used to assess protein levels. Correlations were assessed between the pH of cell culture media throughout manufacturing and cell proliferation as well as clinical outcomes. Next-generation sequencing was conducted to examine gene expression profiles of the final CAR T-cell products.
A pH level at the lower range of normal at the beginning of the manufacturing process significantly correlated with measures of T-cell expansion and metabolism. Stable or rising pH during the manufacturing process was associated with clinical response, whereas a drop in pH was associated with non-response.
pH has potential to serve as an informative factor in predicting CAR T-cell quality and clinical outcomes. Thus, its active monitoring during manufacturing may ensure a more effective CAR T-cell product.
The expansion and persistence of chimeric antigen receptor (CAR) T-cells in patients are associated with response, toxicity, and long-term efficacy. As such, the tools used to detect CAR T-cells ...following infusion are fundamental for optimizing this therapeutic approach. Nevertheless, despite the critical value of this essential biomarker, there is significant variability in CAR T-cell detection methods as well as the frequency and intervals of testing. Furthermore, heterogeneity in the reporting of quantitative data adds layers of complexity that limit intertrial and interconstruct comparisons. We sought to assess the heterogeneity of CAR T-cell expansion and persistence data in a scoping review using the PRISMA-ScR checklist. Focusing on 21 clinical trials from the USA, featuring a Food and Drug Administration-approved CAR T-cell construct or one of its predecessors, 105 manuscripts were screened and 60 were selected for analysis, based on the inclusion of CAR T-cell expansion and persistence data. Across the array of CAR T-cell constructs, flow cytometry and quantitative PCR were identified as the two primary techniques for detecting CAR T-cells. However, despite apparent uniformity in detection techniques, the specific methods used were highly variable. Detection time points and the number of evaluated time points also ranged markedly and quantitative data were often not reported. To evaluate whether subsequent manuscripts from a trial resolved these issues, we analyzed all subsequent manuscripts reporting on the 21 clinical trials, recording all expansion and persistence data. While additional detection techniques–including droplet digital PCR, NanoString, and single-cell RNA sequencing–were reported in follow-up publications, inconsistencies with respect to detection time points and frequency remained, with a significant amount of quantitative data still not readily available. Our findings highlight the critical need to establish universal standards for reporting on CAR T-cell detection, especially in early phase studies. The current reporting of non-interconvertible metrics and limited provision of quantitative data make cross-trial and cross-CAR T-cell construct comparisons extremely challenging. Establishing a standardized approach for collecting and reporting data is urgently needed and would represent a substantial advancement in the ability to improve outcomes for patients receiving CAR T-cell therapies.
Using a multimodal approach toward developing a new CD70-targeted Chimeric antigen receptor (CAR) T cell in acute myeloid leukemia, Leick et al.1 report on their synergetic strategy, which ...incorporates both CAR T cell construct modifications with enhancement of leukemia antigen expression to improve CAR T cell functionality.
Using a multimodal approach toward developing a new CD70-targeted Chimeric antigen receptor (CAR) T cell in acute myeloid leukemia, Leick et al.1 report on their synergetic strategy, which incorporates both CAR T cell construct modifications with enhancement of leukemia antigen expression to improve CAR T cell functionality.
A disease risk index (DRI) that was developed for adults with hematologic malignancy who were undergoing hematopoietic cell transplantation is also being used to stratify children and adolescents by ...disease risk. Therefore, to develop and validate a DRI that can be used to stratify those with AML and ALL by their disease risk, we analyzed 2569 patients aged <18 years with acute myeloid (AML; n = 1224) or lymphoblastic (ALL; n = 1345) leukemia who underwent hematopoietic cell transplantation. Training and validation subsets for each disease were generated randomly with 1:1 assignment to the subsets, and separate prognostic models were derived for each disease. For AML, 4 risk groups were identified based on age, cytogenetic risk, and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2, 3, 5), high (7, 8), and very high (>8) risk groups was 78%, 53%, 40%, and 25%, respectively (P < .0001). For ALL, 3 risk groups were identified based on age and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2-4), and high (≥5) risk groups was 68%, 51%, and 33%, respectively (P < .0001). We confirmed that the risk groups could be applied to overall survival, with 5-year survival ranging from 80% to 33% and 73% to 42% for AML and ALL, respectively (P < .0001). This validated pediatric DRI, which includes age and residual disease status, can be used to facilitate prognostication and stratification of children with AML and ALL for allogeneic transplantation.
•The pediatric DRI stratified children with AML and ALL into clinically distinct risk groups based on pretransplantation information.•Risk stratification was based on age at transplant, cytogenetics, and disease status including minimal residual disease at transplant.
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