Anti-PSMA/CD3 Bispecific Antibody Delivery and Antitumor Activity Using a Polymeric Depot Formulation.
Mol Cancer Ther
; 17(9): 1927-1940, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29891487
ABSTRACT
Small therapeutic proteins represent a promising novel approach to treat cancer. Nevertheless, their clinical application is often adversely impacted by their short plasma half-life. Controlled long-term delivery of small biologicals has become a challenge because of their hydrophilic properties and in some cases their limited stability. Here, an in situ forming depot-injectable polymeric system was used to deliver BiJ591, a bispecific T-cell engager (BiTE) targeting both prostate-specific membrane antigen (PSMA) and the CD3 T-cell receptor in prostate cancer. BiJ591 induced T-cell activation, prostate cancer-directed cell lysis, and tumor growth inhibition. The use of diblock (DB) and triblock (TB) biodegradable polyethylene glycol-poly(lactic acid; PEG-PLA) copolymers solubilized in tripropionin, a small-chain triglyceride, allowed maintenance of BiJ591 stability and functionality in the formed depot and controlled its release. In mice, after a single subcutaneous injection, one of the polymeric candidates, TB1/DB4, provided the most sustained release of BiJ591 for up to 21 days. Moreover, the use of BiJ591-TB1/DB4 formulation in prostate cancer xenograft models showed significant therapeutic activity in both low and high PSMA-expressing tumors, whereas daily intravenous administration of BiJ591 was less efficient. Collectively, these data provide new insights into the development of controlled delivery of small therapeutic proteins in cancer. Mol Cancer Ther; 17(9); 1927-40. ©2018 AACR.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
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Neoplasias da Próstata
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Sistemas de Liberação de Medicamentos
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Anticorpos Biespecíficos
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Ensaios Antitumorais Modelo de Xenoenxerto
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Antineoplásicos
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mol Cancer Ther
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2018
Tipo de documento:
Article