Antitumor activities of agonistic anti-TNFR antibodies require differential FcγRIIB coengagement in vivo.
Proc Natl Acad Sci U S A
; 110(48): 19501-6, 2013 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-24218606
ABSTRACT
Agonistic anti-TNF receptor (TNFR) superfamily member antibodies are a class of promising antitumor therapies in active clinical investigation. An unexpected requirement for inhibitory Fcγ receptor FcγRIIB coengagement has recently been described for their in vivo antitumor activities. Although these findings have informed the design of more potent antitumor agonistic, anti-TNFR therapies, the underlying mechanism has remained obscure. Through detailed genetic analysis of strains conditionally deleted for FcγRIIB on defined cellular populations or mutated in specific signaling components, we now demonstrate that different agonistic anti-TNFR antibodies have specific requirements for FcγRIIB expression on defined cellular populations and function in trans in the absence of FcγRIIB signaling components, thus supporting a general mechanism of FcγRIIB cross-linking in vivo for the activities of these antibodies.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Receptores de IgG
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Receptores do Fator de Necrose Tumoral
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Anticorpos
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2013
Tipo de documento:
Article