Continuous and high level in vivo delivery of endostatin from recombinant cells encapsulated in Theracyte Immunoisolation devices

• Grant number: 10/06569-7
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: June 01, 2010
• End date: November 30, 2010
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ligia Ely Morganti Ferreira Dias
• Grantee: Ligia Ely Morganti Ferreira Dias
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Endostatin is a potent inhibitor of angiogenesis and tumor growth. It has been shown that continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The Theracyte system is a PTFE semi-permeable membrane macro-encapsulation system for implantation of genetically engineered cells for therapeutic proteins delivery in vivo, circumventing the problem of limited half life and variation in circulating levels. Microarchitecture of Theracyte membrane is designed to induce neovascularization at the tissue interface and to protect the cells from host's immune rejection. In a scheme for the Theracyte devices implant, used to enable the neovascularization to occur before endostatin secreted by the cells inside the devices could inhibit this process, the devices were introduced s.c. into SCID mice and after healing (17 days later), CHO cells expressing endostatin were injected within the devices. In another model for devices implantation, the cells expressing endostatin where loaded into immunoisolation devices which were immediately implanted s.c. into mice. High and constant levels of endostatin of up to 3,7 ¼g/ml were detected in plasma of mice in which the devices were pre-implanted, throughout the two months duration of the study. Lower but also constant levels of endostatin (up to 2.1 ¼g/ml plasma) were detected in mice in which the devices were implanted with the cells. Immunohistochemistry using anti-endostatin antibody showed reaction within the device and outside it, demonstrating that endostatin, secreted by the confined recombinant cells, permeated trough the membrane, reaching the surrounding tissues. (AU)