CD19: a biomarker for B cell development, lymphoma diagnosis and therapy

Wang, Kemeng; Wei, Guoqing; Liu, Delong

doi:10.1186/2162-3619-1-36

Cited by 449 publications

(338 citation statements)

References 41 publications

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“…Blinatumomab targets CD3ε on T cells and the cell surface receptor CD19, which is expressed on B cells at all stages of development, both normal and cancerous, and is a reliable B‐cell biomarker 34, 35. The affinity of blinatumomab for CD3 and CD19 is low; K d values for each arm are in the range of 10 −7 M and 10 −9 M, respectively 36, 37.…”

Section: Mechanism Of Action and Key Characteristics Of Bite® Antibodmentioning

confidence: 99%

Translation and Clinical Development of Bispecific T‐cell Engaging Antibodies for Cancer Treatment

Yuraszeck

Kasichayanula

Benjamin

2017

Clin Pharma and Therapeutics

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Bispecific T‐cell Engagers (BiTE®) antibody constructs enable a polyclonal T‐cell response to cell‐surface tumor‐associated antigens, bypassing the narrow specificities of T‐cell receptors and the need for antigen presentation through the major histocompatibility complex pathways. Blinatumomab, a CD19xCD3 BiTE® antibody construct, received accelerated approval for the treatment of relapsed/refractory Philadelphia chromosome negative acute lymphoblastic leukemia. Herein we review the pharmacology, safety, and efficacy observed in studies of blinatumomab and other BiTE® antibody constructs. Quantitative systems pharmacology is envisioned as a means to optimize dosing decisions for trials in which BiTE® antibody constructs are administered as monotherapy or in combination with other immunotherapies.

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Section: Mechanism Of Action and Key Characteristics Of Bite® Antibodmentioning

confidence: 99%

Translation and Clinical Development of Bispecific T‐cell Engaging Antibodies for Cancer Treatment

Yuraszeck

Kasichayanula

Benjamin

2017

Clin Pharma and Therapeutics

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“…CD19 является перспективной мишенью для анти-генспецифической иммунотерапии, поскольку он экспрессируется на поверхности большинства опу-холевых В-клеток [44], в то время как в нормальных тканях экспрессия этого маркера ограничена В-клетками и, предположительно, фолликулярными дендритными клетками [45]. Использование анти-генсвязывающего домена анти-CD19 в составе CAR для адоптивной иммунотерапии позволило получить многообещающие результаты при рецидивах и реф-рактерных В-клеточных неоплазиях [46].…”

Section: Discussionunclassified

Manufacturing of CD19 Specific CAR T-Cells and Evaluation of their Functional Activity in Vitro

Петухов¹,

Маркова²,

Моторин³

et al. 2018

Клиническая онкогематология

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Background. The most promising variant of adoptive immunotherapy of the B-line oncohematological diseases includes the use of cells with the chimeric antigen receptor (CAR T-cells), that showed extraordinary results in clinical studies. Aim. To manufacture CAR T-cells for the clinical use and to study their cytotoxicity in vitro. Methods. Human T-lymphocytes were transduced by the lentiviral vector containing anti-CD19-CAR, RIAD, and GFP genes. The T-cell transduction efficacy was assessed on the basis of GFP protein signal by flow cytometry. Propidium iodide was used to analyse the cell viability. Cytotoxic activity of the manufactured CAR T-cells was studied in the presence of the target cells being directly co-cultivated. Analysis of the number and viability of CAR T-cells and cytokine expression was performed by flow cytometry. Results. The viability of the transduced T-cells and GFP expression reached 91.87 % and 50.87 % respectively. When cultured in the presence of IL-2 and recombinant CD19 (the target antigen), the amount of CAR-T after 120 h of the process was 1.4 times larger compared with the period of 48 h. In the cytotoxic test of co-cultivation CART with the K562-CD19+ cells the percentage of CAR-T increased to 57 % and 84.5 % after 48 h and 120 h of exposure respectively. When cultured with the K562 cells (test line not expressing CD19) the number of CAR T-cells decreased to 36.2 % within 48 h while the number of K562 cells increased to 58.3 %. The viability of target cells in the experimental and control groups was 3.5 % and 36.74 % respectively. Comparison of IL-6 level in the control and experimental groups revealed that the differences are insignificant, as opposed to the level of other cytokines (IFN-y, IL-2, TNF) which proved to be different in both groups. Conclusion. The present work resulted in the production of anti-CD19 CAR T-cells with adequate viability. The in vitro model demonstrated their cytotoxicity. Manufacturing of CAR T-cells for clinical use is the first step of the development of adoptive immunotherapy in the Russian Federation.

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“…48 As with normal B cells, CD19 is expressed at relatively high levels in nearly all B-cell malignancies. 49 The involvement of ERK signaling and c-Myc in CD19 signaling and biological responses haematologica | 2014; 99(12) 19 However, isolated enhanced CD19 expression is independent of B-cell lymphomagenesis, and malignant transformation of GC B cells remains a c-Myc-dependent process. 19 Our results here shed new light on the mechanism by which CD19 mediates the activation of ERK and c-Myc in B-lymphomas.…”

Section: Discussionmentioning

confidence: 99%