PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein.
Nat Commun
; 10(1): 2484, 2019 06 06.
Article
em En
| MEDLINE
| ID: mdl-31171773
ABSTRACT
Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro. PRL3 antigens are detected on the cell surface and outer exosomal membranes, implying an 'inside-out' externalization of PRL3. PRL3-zumab binds to surface PRL3 in a manner consistent with that in classical antibody-dependent cell-mediated cytotoxicity or antibody-dependent cellular phagocytosis tumor elimination pathways, as PRL3-zumab requires an intact Fc region and host FcγII/III receptor engagement to recruit B cells, NK cells and macrophages to PRL3+ tumor microenvironments. PRL3 is overexpressed in 80.6% of 151 fresh-frozen tumor samples across 11 common cancers examined, but not in patient-matched normal tissues, thereby implicating PRL3 as a tumor-associated antigen. Targeting externalized PRL3 antigens with PRL3-zumab may represent a feasible approach for anti-tumor immunotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Fosfatases
/
Carcinoma Hepatocelular
/
Hepatócitos
/
Citofagocitose
/
Microambiente Tumoral
/
Antineoplásicos Imunológicos
/
Neoplasias Hepáticas
/
Citotoxicidade Celular Dependente de Anticorpos
/
Proteínas de Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2019
Tipo de documento:
Article