Continuous and High-Level In Vivo Delivery of Endostatin From Recombinant Cells Encapsulated in TheraCyte (R) Immunoisolation Devices

Autor(es)

Malavasi, N. V. ^[1] ; Rodrigues, D. B. ^[1] ; Chammas, R. ^[2] ; Chura-Chambi, R. M. ^[1] ; Barbuto, J. A. M. ^[3] ; Balduino, K. ^[1] ; Nonogaki, S. ^[4] ; Morganti, L. ^[1]

Afiliação do(s) autor(es)

^[1] Ctr Biotecnol, IPEN, CNEN SP, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Expt Oncol Lab, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, BR-09500900 Sao Paulo - Brazil

^[4] Inst Adolfo Lutz Registro, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELL TRANSPLANTATION; v. 19, n. 3, p. 269-277, 2010.
• Citações Web of Science: 5

Resumo

Endostatin (ES) is a potent inhibitor of angiogenesis and tumor growth. Continuous ES delivery of ES improves the efficacy and potency of the antitumoral therapy. The TheraCyte (R) system is a polytetrafluoroethylene (PTFE) semipermeable membrane macroencapsulation system for implantation of genetically engineered cells specially designed for the in vivo delivery of therapeutic proteins, such as ES, which circumvents the problem of limited half-life and variation in circulating levels. In order to enable neovascularization at the tissues adjacent to the devices prior to ES secretion by the cells inside them, we designed a scheme in which empty TheraCyte (R) devices were preimplanted SC into immunodeficient mice. Only after healing (17 days later) were Chinese hamster ovary cells expressing ES injected into the preimplanted devices. In another model for device implantation, the cells expressing ES where loaded into the immunoisolation devices prior to implantation into the animals, and the TheraCyte (R) were then immediately implanted SC into the mice. Throughout the 2-month study, constant high ES levels of up to 3.7 mu g/ml were detected in the plasma of the mice preimplanted with the devices, while lower but also constant levels of ES (up to 2.1 mu g/ml plasma) were detected in the mice that had received devices preloaded with the ES-expressing cells. Immunohistochemistry using anti-ES antibody showed reaction within the device and outside it, demonstrating that ES, secreted by the confined recombinant cells, permeated through the membrane and reached the surrounding tissues. (AU)

• Processo FAPESP: 00/04658-0 - Células eucariotas recombinantes secretoras de endostatina para tratamento antiogiogênico de tumores: comparação com a administração convencional
• Beneficiário: Ligia Ely Morganti Ferreira Dias
• Modalidade de apoio: Auxílio à Pesquisa - Regular