Cancer therapeutic trispecific antibodies recruiting both T and natural killer cells to cancer cells.
Oncol Rep
; 50(6)2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37859608
ABSTRACT
T cells and natural killer (NK) cells are major effector cells recruited by cancer therapeutic bispecific antibodies; however, differences in the populations of these cells in individual tumors limit the general use of these antibodies. In the present study, trispecific antibodies were created, namely T cell and NK cell engagers (TaKEs), that recruit both T cells and NK cells. Notably, three Fcfused TaKEs were designed, TaKE1Fc, TaKE2Fc and TaKE3Fc, using variable fragments targeting the epidermal growth factor receptor on tumor cells, CD3 on T cells, and CD16 on NK cells. Among them, TaKE1Fc was predicted to form a circular tetrabodylike configuration and exhibited the highest production and greatest cancer growth inhibitory effects. TaKE1 was prepared from TaKE1Fc by digesting the Fc region for further functional evaluation. The resulting TaKE1 exhibited trispecificity via its ability to bind cancer cells, T cells and NK cells, as well as comparable or greater cancer growth inhibitory effects to those of two bispecific antibodies that recruit T cells and NK cells, respectively. A functional trispecific antibody with the potential to exert strong therapeutic effects independent of T cell and NK cell populations was developed.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Biespecíficos
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Oncol Rep
Ano de publicação:
2023
Tipo de documento:
Article