Development of a microfluidic cell transfection device into gene-edited CAR T cell manufacturing workflow

Article Medicine, Research & Experimental

Explorations of CRISPR/Cas9 for improving the long-term efficacy of universal CAR-T cells in tumor immunotherapy

Muhammad Naeem et al.

Summary: The innovative CRISPR/Cas9 technology has the potential to overcome the challenges in CAR-T cell therapy for malignancies and improve antitumor efficacy, providing opportunities for novel cancer immunotherapies.

LIFE SCIENCES (2023)

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Article Biotechnology & Applied Microbiology

CGMP Compliant Microfluidic Transfection of Induced Pluripotent Stem Cells for CRISPR-Mediated Genome Editing

Laura R Bohrer et al.

STEM CELLS (2023)

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Article Immunology

Microfluidic Squeezing Enables MHC Class I Antigen Presentation by Diverse Immune Cells to Elicit CD8+ T Cell Responses with Antitumor Activity

Matthew G. Booty et al.

Summary: Delivery of antigens to the cytosol through microfluidic squeezing enables effective CD8(+) T cell responses, and diverse cell types can present antigens through this approach. This method can successfully prime CD8(+) T cells both in vitro and in vivo.

JOURNAL OF IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells

J. Joseph Melenhorst et al.

Summary: CAR T cells redirected to target CD19 demonstrated long-lasting potential and clonal stability in two patients with chronic lymphocytic leukaemia. Highly activated CD4(+) cells emerged and dominated the CAR T cell population at later time points. These unexpected CAR T cell populations provide novel insights into anti-cancer response and long-term remission in leukaemia.

NATURE (2022)

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Article Multidisciplinary Sciences

In vivo imaging of nanoparticle-labeled CAR T cells

Louise Kiru et al.

Summary: The study introduces a new approach to label CAR T cells with iron oxide nanoparticles, enabling noninvasive detection of the CAR T cells in solid tumors. The results show that labeled CAR T cells could locate to osteosarcomas and off-target sites, while unlabeled cells were not visible. This study provides a new method for monitoring the location of CAR T cells in solid tumors.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Review Oncology

Engineered T Cells: CAR T Cell Therapy and Beyond

P. Connor Johnson et al.

Summary: This review article discusses the current state and future directions of engineered T-cell therapies in non-Hodgkin lymphomas. It provides an overview of the approved CAR T-cell products and other promising engineered T-cell products in development. CAR T-cell therapies have significantly transformed the treatment landscape for relapsed/refractory B cell lymphomas and hold great promise for future clinical use.

CURRENT ONCOLOGY REPORTS (2022)

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Article Engineering, Biomedical

Rapid manufacturing of non-activated potent CAR T cells

Saba Ghassemi et al.

Summary: Non-activated CAR T cells can be generated within 24 hours from T cells derived from peripheral blood, without the need for T-cell activation. This rapid manufacturing method has the potential to reduce production costs and broaden the applicability of CAR T cells.

NATURE BIOMEDICAL ENGINEERING (2022)

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Article Biochemical Research Methods

Scaling microfluidic throughput with flow-balanced manifolds to simply control devices with multiple inlets and outlets

Katherine M. Young et al.

Summary: Microfluidics can provide unique functionalities for cell processing, but balancing processing throughput and cell concentration is crucial. Utilizing multiple parallel channels and a second manifold layer can achieve flow balance, ensuring flow properties in each channel, and enhance processing efficiency.

BIOMICROFLUIDICS (2022)

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Review Biochemistry & Molecular Biology

Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing

Alexander Dimitri et al.

Summary: Chimeric Antigen Receptor (CAR) T-cells have revolutionized personalized cancer therapy, but their effectiveness in many other cancers, especially solid tumors, has not reached its full potential. The use of CRISPR-Cas9 gene editing technology can address the limitations of CAR T-cell therapy and open new avenues for research to optimize its efficacy.

MOLECULAR CANCER (2022)

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Article Multidisciplinary Sciences

Potential solutions for manufacture of CAR T cells in cancer immunotherapy

Ulrich Blache et al.

Summary: CAR T cell therapy is effective in treating cancer, but obstacles in biology and manufacturing hinder its widespread application. New technologies are needed to enable the treatment of larger patient groups.

NATURE COMMUNICATIONS (2022)

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Article Biology

Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Richard Gerum et al.

Summary: This study presents a high-throughput, simple, and low-cost microfluidic method to quantitatively measure the elastic and viscous moduli of individual cells. By measuring cell deformation and rotation frequency, the frequency-dependent viscoelastic properties of cells can be determined, revealing the influence of cell cycle and physical interactions between different cell structures.

ELIFE (2022)

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Review Cell & Tissue Engineering

CAR T cells in solid tumors: challenges and opportunities

Faroogh Marofi et al.

Summary: CAR T cells have shown significant advancements in treating blood disorders, but face challenges in solid tumor therapy due to issues with recognition, trafficking, and survival within the tumor. Efforts to overcome these challenges, including addressing the immunosuppressive tumor microenvironment, show promise in reducing T cell exhaustion and improving therapeutic outcomes in non-hematologic malignancies.

STEM CELL RESEARCH & THERAPY (2021)

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Article Cell Biology

Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity

Brooke Prinzing et al.

Summary: CAR T cell exhaustion occurs due to epigenetic repression of T cell multipotent potential, deletion of DNMT3A enhances CAR T cell functionality and upregulates interleukin-10, and a genome-wide DNA methylation profiling identifies genes targeted for epigenetic silencing that limits immune cell stemness. This epigenetically regulated multipotency program is crucial for the clinical outcome of CAR T cell therapies, highlighting the importance of leveraging epigenetic mechanisms to improve CAR T cell efficacy.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Review Immunology

T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy

Palak H. Mehta et al.

Summary: T cell fitness plays a crucial role in the efficacy of CAR T cell therapy, and factors such as age, chronic infection, malignancy, and treatment may impact T cell health. Tailoring clinical decisions and CTT protocols for patients with severe T cell dysfunction could improve treatment outcomes and methods for T cell collection and delivery.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Biotechnology & Applied Microbiology

Navigating CAR-T cells through the solid-tumour microenvironment

Andrew J. Hou et al.

Summary: CAR-T cells have limited efficacy in treating solid tumors, but various engineering strategies can overcome the obstacles posed by the tumor microenvironment, producing next-generation T cells with enhanced specificity and sustained effector function.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Article Chemistry, Multidisciplinary

Highly Efficient Transfection of Human Primary T Lymphocytes Using Droplet-Enabled Mechanoporation

Byeongju Joo et al.

Summary: The combination of droplet microfluidics and cell mechanoporation can effectively enhance intracellular delivery efficiency, reduce cargo consumption and clogging issues, while maintaining cell viability. This method demonstrates high scalability and superiority over current state-of-the-art cell engineering techniques.

ACS NANO (2021)

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Article Biochemical Research Methods

Numerical simulation of intracellular drug delivery via rapid squeezing

Mehdi Nikfar et al.

Summary: The study aims to develop a three-dimensional computational model to investigate intracellular drug delivery through squeezing. This model does not rely on experimental conditions and device geometry, providing high accuracy.

BIOMICROFLUIDICS (2021)

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Review Cell & Tissue Engineering

A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies

Ehsan Razeghian et al.

Summary: CAR-T cell therapy plays a crucial role in tumor immunotherapy, but its costly and time-consuming manufacturing process can be a limiting factor. Developing universal allogeneic T cells with higher anti-tumor effects is essential. Using genome-editing technologies like CRISPR-Cas9 to create off-the-shelf CAR-T cells with robust resistance to immune cell-suppressive molecules is an important advancement in the field.

STEM CELL RESEARCH & THERAPY (2021)

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Article Chemistry, Multidisciplinary

The Good and the Bad of Cell Membrane Electroporation

Katja Balantic et al.

Summary: Electroporation increases cell membrane permeability through high-voltage electric pulses and is widely used in medicine. It helps the entry or exit of hydrophilic molecules but also poses challenges in research and application.

ACTA CHIMICA SLOVENICA (2021)

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Article Biochemical Research Methods

mRNA-based CAR T-cells manufactured by miniaturized two-step electroporation produce selective cytotoxicity toward target cancer cells

Vidura Jayasooriya et al.

Summary: The study focused on the translation of electroporated mRNA to CAR molecules, time dependent degradation of CAR molecules, and cytotoxicity produced by CAR T-cells on cancer cells. It was found that the initial expression of CAR molecules dictates the cytotoxicity, which can be controlled by experimental parameters such as electroporation time and mRNA concentration in the electroporation buffer. The use of a novel two-step electroporation technique could provide a viable path for producing CAR T-cells with longer cytotoxic lifespans.

LAB ON A CHIP (2021)

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Article Biochemical Research Methods

Efficient and gentle delivery of molecules into cells with different elasticity via Progressive Mechanoporation

Alena Uvizl et al.

Summary: Cell elasticity plays a key role in determining the efficiency of molecule delivery, leading to the development of a novel progressive mechanoporation (PM) method. PM involves multistage cell deformation for improved delivery efficiency into cells of different elasticity, with high-throughput processing and reliable and reproducible cell treatment.

LAB ON A CHIP (2021)

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Article Chemistry, Multidisciplinary

Massively-Parallelized, Deterministic Mechanoporation for Intracellular Delivery

Harish G. Dixitt et al.

NANO LETTERS (2020)

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Article Chemistry, Multidisciplinary

Cell Mechanical and Physiological Behavior in the Regime of Rapid Mechanical Compressions that Lead to Cell Volume Change

Anna Liu et al.

SMALL (2020)

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Article Chemistry, Multidisciplinary

Intracellular Nanomaterial Delivery via Spiral Hydroporation

GeoumYoung Kang et al.

ACS NANO (2020)

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Article Immunology

CD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicity

Faizah Alotaibi et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2020)

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Article Multidisciplinary Sciences

CRISPR-engineered T cells in patients with refractory cancer

Edward A. Stadtmauer et al.

SCIENCE (2020)

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Review Oncology

CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions

Sherly Mardiana et al.

FRONTIERS IN ONCOLOGY (2020)

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Article Chemistry, Multidisciplinary

Microfluidic Cell Stretching for Highly Effective Gene Delivery into Hard-to-Transfect Primary Cells

Jeongsoo Hur et al.

ACS NANO (2020)

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Meeting Abstract Hematology

CRISPR-Cas9 Knock out of CD5 Enhances the Anti-Tumor Activity of Chimeric Antigen Receptor T Cells

Inkook Chun et al.

BLOOD (2020)

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Article Oncology

CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma

Bryan D. Choi et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2019)

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Review Oncology

Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions

Lauren C. Fleischer et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2019)

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Article Biotechnology & Applied Microbiology

Optimized DNA electroporation for primary human T cell engineering

Zhang Zhang et al.

BMC BIOTECHNOLOGY (2018)

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Article Materials Science, Multidisciplinary

Microfluidic generation of transient cell volume exchange for convectively driven intracellular delivery of large macromolecules

Anna Liu et al.

MATERIALS TODAY (2018)

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Article Chemistry, Multidisciplinary

Intracellular Delivery of Nanomaterials via an Inertial Microfluidic Cell Hydroporator

Yanxiang Deng et al.

NANO LETTERS (2018)

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Article Medicine, General & Internal

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

S. L. Maude et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Review Multidisciplinary Sciences

CAR T cell immunotherapy for human cancer

Carl H. June et al.

SCIENCE (2018)

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Article Oncology

Reducing Ex Vivo Culture Improves the Antileukemic Activity of Chimeric Antigen Receptor (CAR) T Cells

Saba Ghassemi et al.

CANCER IMMUNOLOGY RESEARCH (2018)

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Review Engineering, Biomedical

Biomanufacturing for clinically advanced cell therapies

Ayesha Aijaz et al.

NATURE BIOMEDICAL ENGINEERING (2018)

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Article Multidisciplinary Sciences

Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo

Tia DiTommaso et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

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Article Multidisciplinary Sciences

Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection

Justin Eyquem et al.

NATURE (2017)

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Article Multidisciplinary Sciences

CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells

Levi J. Rupp et al.

SCIENTIFIC REPORTS (2017)

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Review Multidisciplinary Sciences

In vitro and ex vivo strategies for intracellular delivery

Martin P. Stewart et al.

NATURE (2016)

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Article Multidisciplinary Sciences

Cascading and Parallelising Curvilinear Inertial Focusing Systems for High Volume, Wide Size Distribution, Separation and Concentration of Particles

B. Miller et al.

SCIENTIFIC REPORTS (2016)

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Article Multidisciplinary Sciences

Ex Vivo Cytosolic Delivery of Functional Macromolecules to Immune Cells

Armon Sharei et al.

PLOS ONE (2015)

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Review Engineering, Biomedical

Electroporation-Based Technologies for Medicine: Principles, Applications, and Challenges

Martin L. Yarmush et al.

ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16 (2014)

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Article Medicine, General & Internal

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia

Shannon L. Maude et al.

NEW ENGLAND JOURNAL OF MEDICINE (2014)

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Article Engineering, Electrical & Electronic

Microfluidic jet injection for delivering macromolecules into cells

A. Adamo et al.

JOURNAL OF MICROMECHANICS AND MICROENGINEERING (2013)

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Article Multidisciplinary Sciences

Stiffness Dependent Separation of Cells in a Microfluidic Device

Gonghao Wang et al.

PLOS ONE (2013)

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Article Cell Biology

CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia

Renier J. Brentjens et al.

SCIENCE TRANSLATIONAL MEDICINE (2013)

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Article Hematology

A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR

Hiroki Torikai et al.

BLOOD (2012)

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Article Multidisciplinary Sciences

Hydrodynamic stretching of single cells for large population mechanical phenotyping

Daniel R. Gossett et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

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Article Medicine, Research & Experimental

Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity

Chuanfeng Wu et al.

Frontiers of Medicine (2011)

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Article Multidisciplinary Sciences

Continuous inertial focusing, ordering, and separation of particles in microchannels

Dino Di Carlo et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2007)

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Article Hematology

Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells

VFI Van Tendeloo et al.

BLOOD (2001)

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Development of a microfluidic cell transfection device into gene-edited CAR T cell manufacturing workflow

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