Immunophenotype of CAR T-cells and associated apheresis products predicts clinical response in a single-center CD22 CAR T-cell therapy trial in B-cell acute lymphoblastic leukemia.

Although CAR T-cell therapy is increasingly used to treat relapsed B-cell acute lymphoblastic leukemia (ALL), 20-30% of patients do not respond, and few clinical predictors of response have been established, especially in the pediatric population. A deeper analysis of CAR T-cell infusion products, along with the apheresis product used as the starting material for CAR T-cell manufacturing, provides valuable insights for predicting clinical outcomes. We analyzed infusion products and CD4/8-selected T-cell starting materials from pediatric and young adult patients on a single-center study with relapsed/refractory B-cell ALL who were undergoing treatment with CD22 CAR T-cells and evaluated differences between T-cells from responders and non-responders (NCT023215612).

Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy.

Background: Chimeric antigen receptor T (CAR-T) cells have significantly advanced the treatment of cancers such as leukemia and lymphoma. Traditionally, T cells are collected from patients through leukapheresis, an expensive and potentially invasive process that requires specialized equipment and trained personnel. Although whole blood collections are much more technically straightforward, whole blood starting material has not been widely utilized for clinical CAR-T cell manufacturing, in part due to lack of manufacturing processes designed for use in a good manufacturing practice (GMP) environment.

Enhanced sensitivity of magnetic field sensing using L-shaped dual Terfenol-D-FBGs based on the Vernier effect and a dual-loop optoelectronic oscillator.

We proposed and successfully validated improved the sensitivity of magnetic field sensing using the Vernier effect in a dual-loop optoelectronic oscillator (OEO) incorporating cascaded L-shaped Terfenol-D-FBGs. Thanks to the time delay introduced by the dispersion compensating fiber (DCF) in the OEO cavity, precise conversion between the sensing FBG wavelength changes and the OEO oscillation frequency can be achieved. The central wavelengths of the sensing Terfenol-D-FBG change along with the magnetic field.

Turn Hood into Good: Recycling Silicon from Mesoporous Silica Nanoparticles through Magnesium Modification to Lower Toxicity and Promote Tissue Regeneration.

Mesoporous silica nanoparticles (MSNs) have gained wide application as excellent carrier materials; however, their limited degradation in the biological system and potential chronic toxicity pose challenges to their clinical applications. Previous studies have focused on optimizing the elimination performance of MSNs; interestingly, silicon has been well-documented as an essential body component. Therefore, converting MSNs into a form readily utilizable by the organism is a way to turn waste into a valuable resource.

Stable isotope-resolved metabolomics analyses of metabolic phenotypes reveal variable glutamine metabolism in different patient-derived models of non-small cell lung cancer from a single patient.

Introduction: Stable isotope tracers have been increasingly used in preclinical cancer model systems, including cell culture and mouse xenografts, to probe the altered metabolism of a variety of cancers, such as accelerated glycolysis and glutaminolysis and generation of oncometabolites. Comparatively little has been reported on the fidelity of the different preclinical model systems in recapitulating the aberrant metabolism of tumors.

Objectives: We have been developing several different experimental model systems for systems biochemistry analyses of non-small cell lung cancer (NSCLC) using patient-derived tissues to evaluate appropriate models for metabolic and phenotypic analyses.

A case report of the metagenomic next-generation sequencing for timely diagnosis of a traveler with nonspecific febrile Q fever.

Q fever is a worldwide distribution disease caused by （）, an obligate intracellular, Gram-negative acidophilic bacterium belonging to γ-proteobacterium. Most patients present with acute Q-fever accompanied by atypical flu-like symptoms, with only 1%-5% of cases may develop into persistent and focally infected foci, mainly manifest as endocarditis, osteomyelitis and prosthetic arthritis. In this case, the patient experienced an unexplained and uninterrupted fever up to 39.

Deciphering the importance of culture pH on CD22 CAR T-cells characteristics.

Background: 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.

Manufacture of CD22 CAR T cells following positive versus negative selection results in distinct cytokine secretion profiles and γδ T cell output.

Chimeric antigen receptor T cells (CART) have demonstrated curative potential for hematological malignancies, but the optimal manufacturing has not yet been determined and may differ across products. The first step, T cell selection, removes contaminating cell types that can potentially suppress T cell expansion and transduction. While positive selection of CD4/CD8 T cells after leukapheresis is often used in clinical trials, it may modulate signaling cascades downstream of these co-receptors; indeed, the addition of a CD4/CD8-positive selection step altered CD22 CART potency and toxicity in patients.

Assessment and comparison of viability assays for cellular products.

Background Aims: Accurate assessment of cell viability is crucial in cellular product manufacturing, yet selecting the appropriate viability assay presents challenges due to various factors. This study compares and evaluates different viability assays on fresh and cryopreserved cellular products, including peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMC) apheresis products, purified PBMCs and cultured chimeric antigen receptor and T-cell receptor-engineered T-cell products.

Methods: Viability assays, including manual Trypan Blue exclusion, flow cytometry-based assays using 7-aminoactinomycin D (7-AAD) or propidium iodide (PI) direct staining or cell surface marker staining in conjunction with 7-AAD, Cellometer (Nexcelom Bioscience LLC, Lawrence, MA, USA) Acridine Orange/PI staining and Vi-CELL BLU Cell Viability Analyzer (Beckman Coulter, Inc, Brea, CA, USA), were evaluated.

Liquid Storage of Peripheral Blood Stem Cell Products: Effects of Time and Temperature on Product Quality.

Unrelated donor peripheral blood stem cell (PBSC) products often require transport to distant locations, which may take up to 72 hours. Temperature is an important variable that can be controlled during PBSC storage or transport; therefore, we studied the impact of temperature on prolonged storage of clinical-grade, mobilized PBSC products. PBSC products were collected by apheresis from 3 granulocyte colony-stimulating factor-mobilized donors, split into 2 PVC blood bags of equal volume, and stored at room temperature (RT) (18°C to 25 ºC) or 4 °C (2°C to 8 ºC) for 96 hours.

Macroalgae culture-induced carbon sink in a large cultivation area of China.

Macroalgae culture-induced carbon sink in sediments has been little investigated. Here, total organic carbon (TOC), total nitrogen (TN), and δC were examined in sediments in a cultivation field of macroalgae (kelp and Gracilariopsis lemaneiformis) in Sansha Bay, Southeast China. Both proxies of C/N (TOC to TN ratio) and δC indicated a multisource of TOC.

Natural γδT17 cell development and functional acquisition is governed by the mTORC2--Maf-controlled mitochondrial fission pathway.

Natural IL-17-producing γδ T cells (γδT17 cells) are unconventional innate-like T cells that undergo functional programming in the fetal thymus. However, the intrinsic metabolic mechanisms of γδT17 cell development remain undefined. Here, we demonstrate that mTORC2, not mTORC1, selectively controls the functional fate commitment of γδT17 cells through regulating transcription factor c-Maf expression.

Effects of extended transport on cryopreserved allogeneic hematopoietic progenitor cell (HPC) product quality and optimal methods to assess HPC stability.

Background: Since the beginning of the COVID-19 pandemic, cryopreservation of hematopoietic progenitor cell (HPC) products has been increasingly used to ensure allogeneic donor graft availability prior to recipient conditioning for transplantation. However, in addition to variables such as graft transport duration and storage conditions, the cryopreservation process itself may adversely affect graft quality. Furthermore, the optimal methods to assess graft quality have not yet been determined.

Optimizing a fully automated and closed system process for red blood cell reduction of human bone marrow products.

Background Aims: Hematopoietic stem cell transplantation using bone marrow as the graft source is a common treatment for hematopoietic malignancies and disorders. For allogeneic transplants, processing of bone marrow requires the depletion of ABO-mismatched red blood cells (RBCs) to avoid transfusion reactions. Here the authors tested the use of an automated closed system for depleting RBCs from bone marrow and compared the results to a semi-automated platform that is more commonly used in transplant centers today.

[Advances and Prospect of Sampling Techniques and Analytical Methods for Trace Elements in the Ocean: Progress of Trace Element Platform Construction in Xiamen University].

Trace elements, which are important chemical components in the ocean, generally refer to those chemical elements with concentrations below 10 μmol·kgin seawater. Some trace elements, such as Fe and Zn, serve as essential micronutrients for marine organisms, which regulate marine primary productivity and are closely related to the biogeochemical cycle of carbon and nitrogen and therefore affect the global environment and climate change. In contrast, some elements, such as Pb, are anthropogenic pollutants largely released by human activities.

Genome-wide profiling of retroviral DNA integration and its effect on clinical pre-infusion CAR T-cell products.

Background: Clinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are the most commonly used vectors in the manufacturing process. However, the integration pattern of these viral vectors and subsequent effect on CAR T-cell products is still unclear.

Performance comparison of two nucleic acid amplification systems for SARS-CoV-2 detection: A multi-center study.

Background: Many rapid nucleic acid testing systems have emerged to halt the development and spread of COVID-19. However, so far relatively few studies have compared the diagnostic performance between these testing systems and conventional detection systems. Here, we performed a retrospective analysis to evaluate the clinical detection performance between SARS-CoV-2 rapid and conventional nucleic acid detection system.

Identification of genomic determinants contributing to cytokine release in immunotherapies and human diseases.

Background: Cytokine release syndrome (CRS) is a strong immune system response that can occur as a result of the reaction of a cellular immunotherapy with malignant cells. While the frequency and management of CRS in CAR T-cell therapy has been well documented, there is emerging interest in pre-emptive treatment to reduce CRS severity and improve overall outcomes. Accordingly, identification of genomic determinants that contribute to cytokine release may lead to the development of targeted therapies to prevent or abrogate the severity of CRS.

Dynamic trafficking patterns of IL-17-producing γδ T cells are linked to the recurrence of skin inflammation in psoriasis-like dermatitis.

Background: Psoriasis recurrence is a clinically challenging issue. However, the underlying mechanisms haven't been fully understood.

Methods: RNAseq analysis from affected skin of psoriatic patients treated with topical glucocorticoid (GC) with different outcomes was performed.

Differential metabolic requirement governed by transcription factor c-Maf dictates innate γδT17 effector functionality in mice and humans.

Cellular metabolism has been proposed to govern distinct γδ T cell effector functions, but the underlying molecular mechanisms remain unclear. We show that interleukin-17 (IL-17)-producing γδ T (γδT17) and interferon-γ (IFN-γ)-producing γδ T (γδT1) cells have differential metabolic requirements and that the rate-limiting enzyme isocitrate dehydrogenase 2 (IDH2) acts as a metabolic checkpoint for their effector functions. Intriguingly, the transcription factor c-Maf regulates γδT17 effector function through direct regulation of IDH2 promoter activity.

Establishment and validation of in-house cryopreserved CAR/TCR-T cell flow cytometry quality control.

Background: Chimeric antigen receptor (CAR) or T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for the treatment of hematologic malignancies and solid tumors. Multiparametric flow cytometry-based assays play a critical role in monitoring cellular manufacturing steps. Since manufacturing CAR/TCR T-cell products must be in compliance with current good manufacturing practices (cGMP), a standard or quality control for flow cytometry assays should be used to ensure the accuracy of flow cytometry results, but none is currently commercially available.

High efficiency closed-system gene transfer using automated spinoculation.

Background: Gene transfer is an important tool for cellular therapies. Lentiviral vectors are most effectively transferred into lymphocytes or hematopoietic progenitor cells using spinoculation. To enable cGMP (current Good Manufacturing Practice)-compliant cell therapy production, we developed and compared a closed-system spinoculation method that uses cell culture bags, and an automated closed system spinoculation method to decrease technician hands on time and reduce the likelihood for microbial contamination.