Genetically Engineered T Cells

2016 ◽  
pp. 121-132
Author(s):  
Hiroaki Ikeda
2021 ◽  
Author(s):  
Moataz Dowaidar

T cells following genome editing and transformation might be detectable in peripheral blood and tumor tissues for a long time, even more than a year. The types and diversity of T-cells in peripheral blood and tumor tissues changed following transfusion of genetically modified T-cells, and some highly suspected T-cells targeting cancer cells grew, increasing the proportion of such cells. Moreover, after getting genetically engineered T cells, anticancer cytokine secretion increased. T cells changed by gene editing have certain functions, at least from an immunological standpoint. The first clinical research using the CRISPR–Cas9 gene editing method for cancer resistance is more complicated: Using CRISPR–Cas9 gene editing technology to concurrently knock out, amplify, activate and reinfuse three genes in human immune cells. This therapeutic strategy is more demanding, because the changed immune cells have a wider target scope. The data suggest that the efficacy of gene editing in immune cells was 15–45%, and the modified cells could survive long in the peripheral blood and tumor tissues of patients. After three or four months, some T-cells became central T-cells. These encouraging findings pave the way for future experimental cancer research utilizing CRISPR technology.


2019 ◽  
Vol 9 ◽  
Author(s):  
Pavlina Chuntova ◽  
Kira M. Downey ◽  
Bindu Hegde ◽  
Neil D. Almeida ◽  
Hideho Okada

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5445
Author(s):  
Pauline Thomas ◽  
Natacha Galopin ◽  
Emma Bonérandi ◽  
Béatrice Clémenceau ◽  
Sophie Fougeray ◽  
...  

Malignant central nervous system tumors are the leading cause of cancer death in children. Progress in high-throughput molecular techniques has increased the molecular understanding of these tumors, but the outcomes are still poor. Even when efficacious, surgery, radiation, and chemotherapy cause neurologic and neurocognitive morbidity. Adoptive cell therapy with autologous CD19 chimeric antigen receptor T cells (CAR T) has demonstrated remarkable remission rates in patients with relapsed refractory B cell malignancies. Unfortunately, tumor heterogeneity, the identification of appropriate target antigens, and location in a growing brain behind the blood–brain barrier within a specific suppressive immune microenvironment restrict the efficacy of this strategy in pediatric neuro-oncology. In addition, the vulnerability of the brain to unrepairable tissue damage raises important safety concerns. Recent preclinical findings, however, have provided a strong rationale for clinical trials of this approach in patients. Here, we examine the most important challenges associated with the development of CAR T cell immunotherapy and further present the latest preclinical strategies intending to optimize genetically engineered T cells’ efficiency and safety in the field of pediatric neuro-oncology.


2013 ◽  
Vol 273 (2) ◽  
pp. 166-181 ◽  
Author(s):  
M. Essand ◽  
A. S. I. Loskog

2020 ◽  
Author(s):  
Alex Lu ◽  
Hui Liu ◽  
Rongye Shi ◽  
Yihua Cai ◽  
Jinxia Ma ◽  
...  

Abstract Background : Genetically engineered T cells have become an important therapy for B-cell malignancies. Measuring the efficiency of vector integration into the T cell genome is important for assessing the potency and safety of these cancer immunotherapies. Methods: A digital droplet polymerase chain reaction (ddPCR) assay was developed and evaluated for assessing the average number of lenti- and retroviral vectors integrated into Chimeric Antigen Receptor (CAR) and T-Cell Receptor (TCR)-engineered T cells. Results: The ddPCR assay consistently measured the concentration of an empty vector in solution and the average number of CAR and TCR vectors integrated into T cell populations. There was a linear relationship between the average vector copy number per cell measured by ddPCR and the proportion of cells transduced as measured by flow cytometry. Similar vector copy number measurements were obtained by different staff using the ddPCR assay, highlighting the assays reproducibility among technicians. Analysis of fresh and cryopreserved CAR-T and TCR engineered T cells yielded similar results. Conclusions: ddPCR is a robust tool for accurate quantitation of average vector copy number in CAR and TCR engineered T-cells. The assay is also applicable to other types of genetically engineered cells including Natural Killer cells and hematopoietic stem cells.


2008 ◽  
Vol 15 (6) ◽  
pp. 382-392 ◽  
Author(s):  
S Li ◽  
J Yang ◽  
F A Urban ◽  
J N MacGregor ◽  
D P M Hughes ◽  
...  

2011 ◽  
Vol 29 (11) ◽  
pp. 550-557 ◽  
Author(s):  
Tristen S. Park ◽  
Steven A. Rosenberg ◽  
Richard A. Morgan

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