Article
Immunology
Karin Teppert, Nora Winter, Vera Herbel, Caroline Brandes, Simon Lennartz, Fabian Engert, Andrew Kaiser, Thomas Schaser, Dominik Lock
Summary: The prognosis for patients with metastatic melanoma is poor and treatment options are limited. However, genetically-engineered T cell therapy targeting CSPG4 shows promise as a potential treatment. Combining a chimeric co-stimulatory receptor (CCR) and a CSPG4-directed chimeric antigen receptor (CAR) enhances the anti-tumor response and provides a new approach for treating metastatic melanoma.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hyatt Balke-Want, Vimal Keerthi, Nikolaos Gkitsas, Andrew G. Mancini, Gavin L. Kurgan, Carley Fowler, Peng Xu, Xikun Liu, Kyle Asano, Sunny Patel, Christopher J. Fisher, Annie K. Brown, Ramya H. Tunuguntla, Shabnum Patel, Elena Sotillo, Crystal L. Mackall, Steven A. Feldman
Summary: CAR-T cells are now the standard of care for certain B cell and plasma cell malignancies, but their access is limited due to high cost and long manufacturing lead times. This study demonstrates a novel method using CRISPR/Cas9 and nanoplasmid DNA to efficiently integrate CAR into T cells, providing a high yield and functional CAR-T cells. This platform has the potential to increase access to CAR-T cell therapies.
Article
Cell Biology
Chantal Lechanteur, Alexandra Briquet, Virginie Bettonville, Etienne Baudoux, Yves Beguin
Summary: The study outlines the upgrade of an existing clinical-grade MSC manufacturing process to comply with GMP standards, including reorganization of key aspects and validation of a new variant for specific disease treatment. While GMP manufacturing of MSC products is feasible in academic settings, large-scale production for phase III trials would require collaboration with industrial partners.
Article
Pharmacology & Pharmacy
Andreia Almeida, Nazende Guenday-Tuereli, Bruno Sarmento
Summary: Nanomedicines are increasingly being explored for their potential in addressing public health issues by pharmaceutical industry. However, standardizing and approving nanomedicines is still a significant challenge. This study demonstrated the successful scale-up production of two chitosan derivatives in pharmaceutical industry, showing the feasibility of producing polymers and polymeric micelles closer to the bedside.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Immunology
Dimitrios L. Wagner, Ulrike Koehl, Markus Chmielewski, Christoph Scheid, Renata Stripecke
Summary: Gene editing technologies offer exciting possibilities for synthetic biology in CAR-T cell engineering and production. Precise insertion of CARs into the genome and combinatorial gene knock-ins and knock-outs can improve therapeutic efficacy of T cells. These technologies also have the potential to increase production efficiency and reduce costs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Bishnu P. De, Sara Cram, Hyunmi Lee, Jonathan B. Rosenberg, Dolan Sondhi, Ronald G. Crystal, Stephen M. Kaminsky
Summary: We have established a sensitive assay to assess the presence of SV40T DNA in AAV vectors produced by HEK293T cells, which demonstrated low levels of a smaller DNA fragment in different AAV serotypes but undetectable full-length SV40T DNA. In vivo analysis also showed no presence of SV40T mRNA. This assay can be used to evaluate the potential SV40T antigen contamination in AAV vectors generated by HEK293T cells.
HUMAN GENE THERAPY
(2023)
Article
Clinical Neurology
Natalia Pozarowszczyk, Iwona Kurkowska-Jastrzebska, Iwona Sarzynska-Dlugosz, Maciej Nowak, Michal Karlinski
Summary: The aim of this study was to assess the consistency between neurologists and physical and rehabilitation medicine physicians in using the Modified Rankin Scale (mRS) to rate post-stroke disability. The results showed a modest agreement in using mRS, but it may be considered sufficient for observational studies or stroke registries.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Jamal Alzubi, Dominik Lock, Manuel Rhiel, Sabrina Schmitz, Stefan Wild, Claudio Mussolino, Markus Hildenbeutel, Caroline Brandes, Julia Rositzka, Simon Lennartz, Simone A. Haas, Kay O. Chmielewski, Thomas Schaser, Andrew Kaiser, Toni Cathomen, Tatjana Cornu
Summary: An automated process was established to produce functional TCR alpha/beta-free CAR T cells at clinical scale by integrating lentiviral transduction with electroporation of TALEN mRNA. The engineered CAR T cells exhibited high purity, good proliferation, maintained T cell memory phenotype, and effectively eliminated CD19-positive tumor cells.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Engineering, Mechanical
Dongrun Liu, Tian Li, Shi Meng, Zhaijun Lu, Mu Zhong
Summary: A comprehensive understanding of car-body vibration characteristics is crucial for developing more reasonable operational safety and discomfort evaluation indicators. However, this topic has received little attention from scholars or research institutions, leading to a lack of clarity regarding car-body vibration characteristics caused by different complex aerodynamic factors. In this study, full-scale tests were conducted from 2014 to 2016 to investigate train car-body vibrations under different conditions. The findings indicate that car-body vibrations under different aerodynamic conditions primarily exhibit low-frequency rolling and traversing motion below 1 Hz, with the primary frequency close to the car-body lower-centre rolling natural frequency. Moreover, operational safety and vibrational comfort evaluations can be considered as coupled under strong wind conditions, and predicting the train's overturning risk by analyzing the car-body roll angle is feasible.
VEHICLE SYSTEM DYNAMICS
(2022)
Article
Biotechnology & Applied Microbiology
Jinhua Chen, Pengfei Jin, Xiaoqi Chen, Qunying Mao, Fanyue Meng, Xinguo Li, Wei Chen, Meizhi Du, Fan Gao, Pei Liu, Xiujuan Li, Changfu Guo, Tingbo Xie, Weiwei Lu, Qingliang Li, Li Li, Xing Yan, Xiang Guo, Hongqiao Du, Xiuling Li, Kai Duan, Fengcai Zhu
Summary: This study evaluated the immunogenicity, safety, and lot-to-lot consistency of an inactivated EV71 vaccine cultured in bioreactors with different specifications after full immunization. The vaccine was found to be highly immunogenic and safe in children aged 6-35 months, and the six consecutive batches produced by the two bioreactors were consistent.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2022)
Article
Engineering, Electrical & Electronic
Wenzhen Zhang, Yankun Cao, Xifeng Hu, Jia Mi, Pengfei Zhang, Subhas Chandra Mukhopadhyay, Yujun Li, Zhi Liu
Summary: In this study, a comprehensive IVUS Analysis Toolbox (IAT) is developed to automatically extract more image information through the image segmentation model of intravascular ultrasound (ISM-IVUS), allowing experts to modify suboptimal segmentation results and support the calculation and acquisition of instantaneous parameters. Compared to existing IVUS segmentation algorithms, ISM-IVUS better utilizes expert prior knowledge to improve segmentation results.
IEEE TRANSACTIONS ON INSTRUMENTATION AND MEASUREMENT
(2023)
Article
Medicine, Research & Experimental
Jara J. Joedicke, Ulrich Grosskinsky, Kerstin Gerlach, Annette Kuenkele, Uta E. Hoepken, Armin Rehm
Summary: This study successfully improved the production of BCMA CAR T cells by increasing the input of T-SCM/T-CM cells, achieving efficient retroviral transduction and high yield of CAR T cells.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Public, Environmental & Occupational Health
Dainelys Garcia, Angela M. Blizzard, Abigail Peskin, W. Andrew Rothenberg, Ellyn Schmidt, Jennifer Piscitello, Natalie Espinosa, Hanan Salem, Gabriela M. Rodriguez, Jamie A. Sherman, Meaghan V. Parlade, Alexis L. Landa, Eileen M. Davis, Allison Weinstein, Angela Garcia, Camille Perez, Jessica M. Rivera, Chary Martinez, Jason F. Jent
Summary: This study documents the rapid transition from clinic-based intervention to virtual services in response to the COVID-19 pandemic, with I-PCIT demonstrating positive effects on child behavior, caregiver stress, parenting skills, and child compliance. Locally developed strategies, such as online communities of practice and training videos, were found to have the greatest impact on outcomes.
PREVENTION SCIENCE
(2021)
Article
Pediatrics
Riyo Ueda, Yoshimi Kaga, Yosuke Kita, Eiji Nakagawa, Takashi Okada, Masumi Inagaki
Summary: The study found that poorer reading and writing achievement was associated with poorer reading ability in the higher FSIQ group, while in the lower FSIQ group, poorer reading and writing achievement were associated with older age rather than poor reading ability.
Article
Nutrition & Dietetics
Jia-ying Zhang, Chen Niu, Qian Zhang, Meng-jing Wang, Li Ni, Jing-fang Liu, Xing-yu Rong, Chao Zhao, Jing Chen
Summary: This study examined the effects of a low phosphorus diet on phosphorus, calcium, and magnesium metabolism in healthy adult men. The results showed that the low phosphorus diet led to decreased serum and urinary phosphorus levels, increased serum calcium and vitamin D levels, and changes in the intestinal microbiome composition.
JOURNAL OF RENAL NUTRITION
(2021)
Review
Biochemistry & Molecular Biology
Laura Gehrcken, Tatjana Sauerer, Niels Schaft, Jan Doerrie
Summary: Merkel cell carcinoma is a rare and aggressive skin cancer, predominantly caused by Merkel cell polyomavirus or UV light. Checkpoint inhibitor therapies like PD-1/PD-L1 inhibitors show promise in treating metastatic MCC, but some patients do not respond due to diverse immune-related adverse events caused by various mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Astrid Strack, Andrea Deinzer, Christian Thirion, Silke Schroedel, Jan Doerrie, Tatjana Sauerer, Alexander Steinkasserer, Ilka Knippertz
Summary: In this study, the use of LentiBOOST(R)/Polybrene significantly improved the transduction rate of HAdV-5 in various immune cells in both mice and humans, without affecting their phenotype and function.
Article
Immunology
Elias A. T. Koch, Niels Schaft, Mirko Kummer, Carola Berking, Gerold Schuler, Kenichiro Hasumi, Jan Doerrie, Beatrice Schuler-Thurner
Summary: Uveal melanoma is a rare disease with poor response to traditional therapies. Researchers designed a trial using personalized dendritic cell vaccines to activate the immune system and potentially improve clinical outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Xin Lai, Christine Keller, Guido Santos, Niels Schaft, Jan Doerrie, Julio Vera
Summary: Dendritic cells (DCs) can be used for therapeutic vaccination against cancer. Computational modeling can improve our understanding of the molecular mechanisms underlying DC-induced CTL response and help identify new strategies to improve therapeutic DC vaccination for cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Caroline Voskens, Diane Stoica, Marita Rosenberg, Francesco Vitali, Sebastian Zundler, Marion Ganslmayer, Heike Knott, Manuel Wiesinger, Jutta Wunder, Mirko Kummer, Britta Siegmund, Elisabeth Schnoy, Timo Rath, Arndt Hartmann, Holger Hackstein, Beatrice Schuler-Thurner, Carola Berking, Gerold Schuler, Raja Atreya, Markus F. Neurath
Summary: This study reports a successful case of adoptive transfer of ex vivo expanded Tregs in a patient with refractory UC, showing positive responses. These findings suggest that adoptive Treg therapy might be effective in refractory UC.
Review
Biochemistry & Molecular Biology
Amke C. Beenen, Tatjana Sauerer, Niels Schaft, Jan Doerrie
Summary: PD-L1 is a transmembrane protein that plays a crucial role in immune modulation. It interacts with its receptor PD-1 to induce an immune-suppressive signal, regulating the activity of T cells and other effector cells. Apart from its application in cancer therapy, the role of PD-L1 in healthy tissue and non-cancerous diseases has been largely overlooked.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Dennis Christoph Harrer, Charlotte Schenkel, Carola Berking, Wolfgang Herr, Hinrich Abken, Jan Doerrie, Niels Schaft
Summary: In this study, the FDA-approved drug decitabine was used to upregulate the expression of CSPG4 in ovarian carcinoma cells, expanding the repertoire of targetable antigens. The results demonstrated the potential of CSPG4 as an inducible antigen for CAR-T cells in ovarian cancer.
Article
Multidisciplinary Sciences
Lukas Heger, Lukas Hatscher, Chunguang Liang, Christian H. K. Lehmann, Lukas Amon, Jennifer J. Luehr, Tomasz Kaszubowski, Rayk Nzirorera, Niels Schaft, Jan Doerrie, Pascal Irrgang, Matthias Tenbusch, Meik Kunz, Eileen Socher, Stella E. Autenrieth, Ariawan Purbojo, Horia Sirbu, Arndt Hartmann, Christoph Alexiou, Robert Cesnjevar, Diana Dudziak
Summary: Dendritic cells (DCs) are important regulators of immune responses, and can be classified into different types. One type of human DCs, called cDC1, can be distinguished based on the expression of XCR1. XCR1(+) cDC1 have a pre-activated phenotype, secrete high levels of inflammatory cytokines and chemokines upon stimulation, and are efficient in activating NK cells as well as inhibiting replication of Influenza A virus. XCR1(-) cDC1, on the other hand, may represent a late immediate precursor of cDC1 and secrete comparable level of inflammatory cytokines after differentiation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Felix Pfister, Jan Doerrie, Niels Schaft, Vera Buchele, Harald Unterweger, Lucas R. Carnell, Patrick Schreier, Rene Stein, Marketa Kubankova, Jochen Guck, Holger Hackstein, Christoph Alexiou, Christina Janko
Summary: The influence of superparamagnetic iron oxide nanoparticles (SPIONs) on primary human T cells and their potential for magnetically targeted adoptive T cell therapy were investigated in this study. Results showed that SPION-loading did not affect the mechanics and functionality of T cells, indicating its potential for magnetically enriching T cells in solid tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Gastroenterology & Hepatology
Tanja M. Mueller, Li-Juan Liu, Tina Czerwinski, Manuel Wiesinger, Mark Dedden, Eva-Maria Paap, Karen A. -M. Ullrich, Imke Atreya, Britta Siegmund, Raja Atreya, Ben Fabry, Carola Berking, Markus F. Neurath, Sebastian Zundler, Caroline J. Voskens
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Dennis Christoph Harrer, Jan Doerrie, Niels Schaft
Summary: The development of CAR-T cells has revolutionized cancer immunotherapy, but there are challenges such as relapse or refractory disease in some patients, especially those with solid tumors. Obstacles to successful CAR-T cell therapy include antigen shutdown and CAR-T cell dysfunctionality. This review highlights different approaches, including combining CAR-T cells with drugs, to overcome these obstacles and improve the efficacy of CAR-T cell therapy in both hematological malignancies and solid tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)