Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies.
Science
; 341(6141): 88-91, 2013 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-23722425
ABSTRACT
CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with about a 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own. Instead, they exhibited remarkable synergy with all tumor-specific monoclonal antibodies tested by increasing phagocytosis in vitro and enhancing antitumor responses in vivo. This "one-two punch" directs immune responses against tumor cells while lowering the threshold for macrophage activation, thereby providing a universal method for augmenting the efficacy of therapeutic anticancer antibodies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores Inmunológicos
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Antígenos de Diferenciación
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Adyuvantes Inmunológicos
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Antígeno CD47
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Anticuerpos Monoclonales
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Anticuerpos Antineoplásicos
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Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos