Effects of complement and serum IgG on rituximab-dependent natural killer cell-mediated cytotoxicity against Raji cells.
Oncol Lett
; 17(1): 339-347, 2019 Jan.
Article
en En
| MEDLINE
| ID: mdl-30655772
ABSTRACT
Accumulating evidence indicates that the anti-CD20 monoclonal antibody rituximab significantly improves the clinical prognosis of patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. However, a number of patients relapse or fail to respond to rituximab. To further understand the cause of this, polymorphisms of FcγRIIIa were initially detected in healthy volunteers. Subsequently, the rituximab-dependent natural killer (NK) cell-mediated cytotoxicity of different FcγRIIIa genotypes was assessed by a cytotoxicity assay in vitro. Ultimately, the effect of human serum immunoglobulin (Ig) G and complement on rituximab-dependent NK cell-mediated cytotoxicity was evaluated in vitro. It was revealed that FcγRIIIa polymorphisms were associated with the antibody-dependent cell-mediated cytotoxicity (ADCC) of NK cells. In addition, the ADCC of NK cells with FcγRIIIa-158 V/V was increased compared with that of FcγRIIIa-158 V/F. The serum IgG and rituximab Fc segment was able to bind competitively with NK cell FcγRIIIa. It was observed that serum IgG inhibited, whereas complement enhanced rituximab-induced NK-cell mediated ADCC. Therefore, various agents administered synchronously with rituximab may modulate the efficacy of this agent and ultimately its toxicity against tumor cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Oncol Lett
Año:
2019
Tipo del documento:
Article