Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies

Picanço‐Castro, Virgínia; Moço, Pablo Diego; Mizukami, Amanda; Vaz, Leticia Delfini; Pereira, Marcelo de Souza Fernandes; Silvestre, Renata Nacasaki; Costa, Thalita Cristina de Mello; Bomfim, Aline de Sousa; Abreu-Neto, Mário Soares; Malmegrim, Kelen Cristina Ribeiro; Swiech, Kamilla; Covas, Dimas Tadeu

doi:10.1016/j.htct.2019.06.007

Cited by 18 publications

(16 citation statements)

References 26 publications

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“…As mentioned previously, the timing of electroporation relative to T cell activation is a particularly important variable, since proliferating cells achieve much higher transfection efficiencies than resting cells 30 . A wide array of studies have shown a range of optimum times for electroporation post‐activation, but 1–3 days post‐activation appears to be the consensus for viral and non‐viral methods 30,60,61 . A variety of studies also agree that the precise voltage applied to T cells can directly affect transfection efficiency, but the optimal voltage varies significantly between different studies depending on the electroporation system that is being used and other variables.…”

Section: Relevant Aspects Of T Cell Biologymentioning

confidence: 99%

“…30 A wide array of studies have shown a range of optimum times for electroporation post-activation, but 1-3 days post-activation appears to be the consensus for viral and non-viral methods. 30,60,61 A variety of studies also agree that the precise voltage applied to T cells can directly affect transfection efficiency, but the optimal voltage varies significantly between different studies depending on the electroporation system that is being used and other variables. A general range of 300-500 V is used in most of the studies shown in Table 1, since transfection efficiency and viability tend to decrease dramatically above 500 V. 50 Another benefit of electroporation is that a variety of cargoes can be delivered to the cell, including DNA, mRNA, and proteins.…”

Section: Electroporation Of T Cellsmentioning

confidence: 99%

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Optimization of electroporation and other non‐viral gene delivery strategies for T cells

Harris

Elmer

2020

Biotechnology Progress

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CART therapy is a particularly effective treatment for some types of cancer that uses retroviruses to deliver the gene for a chimeric antigen receptor (CAR) to a patient's T cells ex vivo. The CAR enables the T cells to bind and eradicate cells with a specific surface marker (e.g., CD19 + B cells) after they are transfused back into the patient. This treatment was proven to be particularly effective in treating non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL), but the current CART cell manufacturing process has a few significant drawbacks. For example, while lentiviral and gammaretroviral transduction are both relatively effective, the process of producing viral vectors is time-consuming and costly. Additionally, patients must undergo follow up appointments for several years to monitor them for any unanticipated side effects associated with the virus. Therefore, several studies have endeavored to find alternative non-viral gene delivery methods that are less expensive, more precise, simple, and safe. This review focuses on the current state of the most promising non-viral gene delivery techniques, including electroporation and transfection with cationic polymers or lipids.

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Section: Relevant Aspects Of T Cell Biologymentioning

confidence: 99%

Section: Electroporation Of T Cellsmentioning

confidence: 99%

Optimization of electroporation and other non‐viral gene delivery strategies for T cells

Harris

Elmer

2020

Biotechnology Progress

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“…Later, additional co-stimulatory domains, like CD28, 4-1BB, CD27, ICOS, and/or OX40, were added to the CAR individually or in combination (called second-/third-generation CAR-T cells) and have resulted in better persistence, robust activation, and enhanced anti-tumor activity [ 10 ]. CARs are mainly transduced by viral methods, with lentiviral transduction being the most common method [ 11 ]. Other non-viral transduction methods have emerged that utilize the DNA or mRNA transposon systems and have proved to be less mutagenic [ 12 ].…”

Section: Overview Of Car-t Cellsmentioning

confidence: 99%

Innovative CAR-T Cell Therapy for Solid Tumor; Current Duel between CAR-T Spear and Tumor Shield

Ali

Shim

et al. 2020

Cancers

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Novel engineered T cells containing chimeric antigen receptors (CAR-T cells) that combine the benefits of antigen recognition and T cell response have been developed, and their effect in the anti-tumor immunotherapy of patients with relapsed/refractory leukemia has been dramatic. Thus, CAR-T cell immunotherapy is rapidly emerging as a new therapy. However, it has limitations that prevent consistency in therapeutic effects in solid tumors, which accounts for over 90% of all cancer patients. Here, we review the literature regarding various obstacles to CAR-T cell immunotherapy for solid tumors, including those that cause CAR-T cell dysfunction in the immunosuppressive tumor microenvironment, such as reactive oxygen species, pH, O2, immunosuppressive cells, cytokines, and metabolites, as well as those that impair cell trafficking into the tumor microenvironment. Next-generation CAR-T cell therapy is currently undergoing clinical trials to overcome these challenges. Therefore, novel approaches to address the challenges faced by CAR-T cell immunotherapy in solid tumors are also discussed here.

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“…As CAR-T cells recognize cell surface molecules without the help of human leukocyte antigen expression, antigen recognition of CARs is not restricted by MHC, and CAR-T cell may recognize almost all types of antigens like carbohydrates, lipids, and proteins [27]. Expansion CAR-T cells in a large scale for clinical use may be challengeable, which can be solved by a cell culture platform [58,59].…”

Section: Future Prospectsmentioning

confidence: 99%

Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

Chen

Sun

Liu

et al. 2019

Journal of Immunology Research

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Chimeric antigen receptor T (CAR-T) cells are T cells engineered to express specific synthetic antigen receptors that can recognize antigens expressed by tumor cells, which after the binding of these antigens to the receptors are eliminated, and have been adopted to treat several kinds of malignancies. Autoimmune diseases (AIDs), a class of chronic disease conditions, can be broadly separated into autoantibody-mediated and T cell-mediated diseases. Treatments for AIDs are focused on restoring immune tolerance. However, current treatments have little effect on immune tolerance inverse; even the molecular target biologics like anti-TNFα inhibitors can only mildly restore immune balance. By using the idea of CAR-T cell treatment in tumors, CAR-T cell-derived immunotherapies, chimeric autoantibody receptor T (CAAR-T) cells, and CAR regulatory T (CAR-T) cells bring new hope of treatment choice for AIDs.

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Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies

Cited by 18 publications

References 26 publications

Optimization of electroporation and other non‐viral gene delivery strategies for T cells

Optimization of electroporation and other non‐viral gene delivery strategies for T cells

Innovative CAR-T Cell Therapy for Solid Tumor; Current Duel between CAR-T Spear and Tumor Shield

Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

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