2021
DOI: 10.3390/v13081528
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Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives

Abstract: Lentiviral vectors have played a critical role in the emergence of gene-modified cell therapies, specifically T cell therapies. Tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta) and most recently brexucabtagene autoleucel (Tecartus) are examples of T cell therapies which are now commercially available for distribution after successfully obtaining EMA and FDA approval for the treatment of blood cancers. All three therapies rely on retroviral vectors to transduce the therapeutic chimeric antigen rec… Show more

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Cited by 73 publications
(38 citation statements)
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“…CAR T cells spread most into hematologic tissues, where they may help eliminate the malignancies of the hematologic system. This study did not compare the distributions of CD19pbCAR T cells with CD19lvCAR T cells because previous studies have evaluated the distribution of lentiviral vectors for T-cell engineering ( 20 ). Better understanding of the properties of CD19pbCAR T may enable the design of more economical cellular medicines for cancer therapy.…”
Section: Discussionmentioning
confidence: 99%
“…CAR T cells spread most into hematologic tissues, where they may help eliminate the malignancies of the hematologic system. This study did not compare the distributions of CD19pbCAR T cells with CD19lvCAR T cells because previous studies have evaluated the distribution of lentiviral vectors for T-cell engineering ( 20 ). Better understanding of the properties of CD19pbCAR T may enable the design of more economical cellular medicines for cancer therapy.…”
Section: Discussionmentioning
confidence: 99%
“…The large-scale bioprocessing of LVs has in recent years adopted the use of bioreactors for perfusion transfection and culture of adherent and suspension cells. Several advances were obtained with the downstream processing of the viral particles with purification technologies (such as tangential flow filtration) (36,37). Quality control (QC) of SIN-LVs is well established and includes: Vector identity (qPCR), Vector concentration/titer (ELISA), Vector functional titer (flow cytometry), residual plasmid DNA (VSV-G DNA qPCR), Residual host DNA (antigen-specific qPCR), detection of replication competent lentivirus (RCL), quantification of residual Benzonase (ELISA), total protein measurements (protein assay), microbiological control (bacteria and fungi assay), detection of endotoxin (LAL assay) as well as volume, pH and appearance (36).…”
Section: Large-scale Manufacturing Of Clinical-grade Rvs/lvsmentioning
confidence: 99%
“…Several obstacles still limit the applicability of large scale use of clinical LVs for medical care. The high costs of LVs for production of T cell therapies, is an important bottle-neck contributing to exorbitant costs of the cell products for a single treatment course (currently >300.000 US dollars in the United States) (37). Further, due to the currently limited manufacturing capacity for LVs, the commercially available CAR-T cell therapies are only regarded as a second-, third-or fourth-line therapeutic option for patients failing to respond to, or have relapsed after conventional therapies (37).…”
Section: Large-scale Manufacturing Of Clinical-grade Rvs/lvsmentioning
confidence: 99%
“…In the present study, we used lentiviral vector to carry cDNA encoding αCD133-αCD3 engager to create the engineered lentiviruses, and to transduce them into healthy donor T cells [ 40 ]. The lentivirus system is safe and widely used to generate many CAR T cells, and commercially available anti-CD19 CAR T cells based on the lentivirus system have been approved by US FDA [ 41 ].…”
Section: Discussionmentioning
confidence: 99%