Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia.
Leukemia
; 34(4): 1102-1115, 2020 04.
Article
de En
| MEDLINE
| ID: mdl-31745215
ABSTRACT
We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective "off-the-shelf" immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Agranulocytes
/
Cellules tueuses naturelles
/
Leucémie-lymphome lymphoblastique à précurseurs B
/
Immunothérapie adoptive
/
Antigènes CD19
/
Thérapie cellulaire et tissulaire
/
Récepteurs chimériques pour l'antigène
Limites:
Animals
/
Humans
Langue:
En
Journal:
Leukemia
Sujet du journal:
HEMATOLOGIA
/
NEOPLASIAS
Année:
2020
Type de document:
Article
Pays d'affiliation:
Italie