Combinatorial targeting of multiple myeloma by complementing T cell engaging antibody fragments.
Commun Biol
; 4(1): 44, 2021 01 08.
Article
em En
| MEDLINE
| ID: mdl-33420283
ABSTRACT
Bispecific T cell engaging antibodies (BiTEs) address tumor associated antigens that are over-expressed on cancer but that can also be found on healthy tissues, causing substantial on-target/off-tumor toxicities. To overcome this hurdle, we recently introduced hemibodies, a pair of complementary antibody fragments that redirect T cells against cancer-defining antigen combinations. Here we show that hemibodies addressing CD38 and SLAMF7 recruit T cells for the exquisite elimination of dual antigen positive multiple myeloma cells while leaving single antigen positive bystanders unharmed. Moreover, CD38 and SLAMF7 targeting BiTEs, but not hemibodies induce massive cytokine release and T cell fratricide reactions, a major drawback of T cell recruiting strategies. Together, we provide evidence in vitro and in vivo that hemibodies can be developed for the effective and highly specific immunotherapy of multiple myeloma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
ADP-Ribosil Ciclase 1
/
Família de Moléculas de Sinalização da Ativação Linfocitária
/
Imunoterapia
/
Mieloma Múltiplo
Tipo de estudo:
Evaluation_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article