Apoptosis of CD19+ chimeric antigen receptor T cells after treatment with chemotherapeutic agents.
Mol Med Rep
; 18(1): 179-183, 2018 Jul.
Article
em En
| MEDLINE
| ID: mdl-29749441
ABSTRACT
The use of chemotherapeutic agents prior to treatment with infusion of cluster of differentiation (CD)19-chimeric antigen receptor (CAR)T cells is important for the efficacy of clinical therapies against hematological malignancies. However, the effect of chemotherapeutic agents on CD19CART cells and the associated underlying mechanisms remain unknown. The first aim of the present study was to determine the effect of chemotherapeutic agents on CART cells using the in vitro Cell Counting kit 8 assay. The second aim was to evaluate the abilities of fludarabine (FDR) and mafosfamide (MFA; a metabolite of cyclophosphamide) to induce apoptosis of CD19CART cells via the use of Annexin V/propidium iodide double staining. In addition, a JC1 fluorescent probe was used to detect alterations in cell membrane potential, and flow cytometry analysis was used to measure concentrations of caspase3/7 to identify apoptotic pathways of CD19CART cells. The data of the present study suggested that FDR and MFA inhibit the activities of CD19CART cells. Alterations to the mitochondrial membrane potential and an increase in the concentration of caspase3/7 indicated early apoptosis of FDR and MFAtreated CD19CART cells. The present study laid a theoretical foundation for the development of programs for clinical treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Apoptose
/
Antígenos CD19
/
Potenciais da Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article