Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells.
Elife
; 92020 07 07.
Article
em En
| MEDLINE
| ID: mdl-32633234
ABSTRACT
Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1-dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Antígeno B7-H1
/
Carcinoma de Células Escamosas de Cabeça e Pescoço
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos