Antibody-dependent cellular cytotoxicity-null effector developed using mammalian and plant GlycoDelete platform.
Sci Rep
; 12(1): 19030, 2022 11 08.
Article
en En
| MEDLINE
| ID: mdl-36347901
ABSTRACT
Cancer therapy using immune checkpoint inhibitor antibodies has markedly shifted the paradigm of cancer treatment. However, methods completely eliminating the effector function of these signal-regulating antibodies is urgently required. The heterogeneity of glycan chains in antibodies limits their use as therapeutic agents due to their variability; thus, the development of uniform glycan chains is necessary. Here, we subjected the anti-programmed cell death protein (PD)-1 antibody nivolumab, a representative immune checkpoint inhibitor, to GlycoDelete (GD) engineering to remove the antibody-dependent cellular cytotoxicity (ADCC) of the antibody, leaving only one glycan in the Fc. Glyco-engineered CHO cells were prepared by overexpressing endo-ß-N-acetyl-glucosaminidase (Endo T) in CHO cells, in which N-acetyl-glucosaminyl-transferase I was knocked out using Cas9. GD IgG1 nivolumab and GD IgG4 nivolumab were produced using GD CHO cells, and glycan removal was confirmed using mass spectrometry. Target binding and PD-1 inhibition was not altered; however, ADCC decreased. Furthermore, the IgG4 form, determined to be the most suitable form of GD nivolumab, was produced in a plant GD system. The plant GD nivolumab also reduced ADCC without affecting PD-1 inhibitory function. Thus, CHO and plant GD platforms can be used to improve signal-regulating antibodies by reducing their effector function.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos Fc de Inmunoglobulinas
/
Nivolumab
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2022
Tipo del documento:
Article