Bi-specific ligand-controlled chimeric antigen receptor T-cell therapy for non-small cell lung cancer.
Biosci Trends
; 12(3): 298-308, 2018 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-29899195
ABSTRACT
Our goal is to develop a switch-controlled approach to enable better control of reactivity and safety of chimeric antigen receptor (CAR)-T therapy for non-small-cell lung cancer (NSCLC). Lentiviral transduction was performed to generate anti-FITC CAR-T cells and target cells stably expressing either isoform of the folate receptor. Colorimetric-based cytotoxic assay, enzyme-linked immunosorbent assay, and multiparametric flow cytometry analysis were used to evaluate the specificity and activity of CAR-T cells in vitro. Human primary T cells stably expressing the fully human anti-FITC CAR were generated. Anti-FITC CAR-T cells displayed antigen-specific and folate-FTIC dependent reactivity against engineered A549-FRα and THP-1-FRß. The selective activation and proliferation of anti-FITC CAR-T cells in vitro stringently relied on the co-existence of folate-FITC and FR- expressing target cells and was dose-titratable with the folate-FITC switch. The excellent in vitro efficacy and specificity of an adaptor-controlled CAR-T therapy to target both tumor cells and tumor-associated macrophages in NSCLCs were validated.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
Biosci Trends
Assunto da revista:
BIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article