A new approach to CAR T cell gene engineering using piggyBac transposon and cultivation in the presence of IL-4, IL-7 and IL-21

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023736%3A_____%2F18%3A00011906" target="_blank" >RIV/00023736:_____/18:00011906 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.jcyt.2017.10.001" target="_blank" >https://doi.org/10.1016/j.jcyt.2017.10.001</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jcyt.2017.10.001" target="_blank" >10.1016/j.jcyt.2017.10.001</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A new approach to CAR T cell gene engineering using piggyBac transposon and cultivation in the presence of IL-4, IL-7 and IL-21

Popis výsledku v původním jazyce

Clinical-grade CAR19 T cells are routinely manufactured by lentiviral/retroviral (LV/RV) transduction of an anti-CD3/CD28 activated T cells which are then propagated in a culture medium supplemented with IL-2. The use of LV/RVs for T cell modification represents a manufacturing challenge due to the complexity of the transduction approach and the necessity of a thorough quality control.
We present here a significantly improved protocol for CAR19 T cell manufacture which is based on the electroporation of PBMCs with plasmid DNA encoding the piggyBac transposon/transposase vectors and their cultivation in the presence of cytokines IL-4, IL-7 and IL-21. We found that activation of CAR receptor either by its cognate ligand (i.e. CD19 expressed on the surface of B cells) or by anti-CAR antibody followed by cultivation in the presence of cytokines IL-4 and IL-7 enables strong and highly selective expansion of functional CAR19 T cells resulting in more than 90% CAR+T cells.

Název v anglickém jazyce

A new approach to CAR T cell gene engineering using piggyBac transposon and cultivation in the presence of IL-4, IL-7 and IL-21

Popis výsledku anglicky

Clinical-grade CAR19 T cells are routinely manufactured by lentiviral/retroviral (LV/RV) transduction of an anti-CD3/CD28 activated T cells which are then propagated in a culture medium supplemented with IL-2. The use of LV/RVs for T cell modification represents a manufacturing challenge due to the complexity of the transduction approach and the necessity of a thorough quality control.
We present here a significantly improved protocol for CAR19 T cell manufacture which is based on the electroporation of PBMCs with plasmid DNA encoding the piggyBac transposon/transposase vectors and their cultivation in the presence of cytokines IL-4, IL-7 and IL-21. We found that activation of CAR receptor either by its cognate ligand (i.e. CD19 expressed on the surface of B cells) or by anti-CAR antibody followed by cultivation in the presence of cytokines IL-4 and IL-7 enables strong and highly selective expansion of functional CAR19 T cells resulting in more than 90% CAR+T cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/NV15-34498A" target="_blank" >NV15-34498A: Vývoj nových metod buněčné a genové terapie hematologických malignit</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cytotherapy: the journal of cell therapy

ISSN

1465-3249

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

507-520

Kód UT WoS článku

000430446900003

EID výsledku v databázi Scopus

2-s2.0-85042195710