Anti-tumor therapy with macroencapsulated endostatin producer cells

<p>Abstract</p> <p>Background</p> <p>Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of lim...

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Main Authors: Balduino Keli N, Chura-Chambi Rosa M, da Costa Patrícia LN, Malavasi Natália V, Chammas Roger, Rodrigues Danielle B, Morganti Ligia
Format: Article
Language:English
Published: BMC 2010-03-01
Series:BMC Biotechnology
Online Access:http://www.biomedcentral.com/1472-6750/10/19
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spelling doaj-96d31689864b49d3b71ce9593816f2782020-11-25T01:42:42ZengBMCBMC Biotechnology1472-67502010-03-011011910.1186/1472-6750-10-19Anti-tumor therapy with macroencapsulated endostatin producer cellsBalduino Keli NChura-Chambi Rosa Mda Costa Patrícia LNMalavasi Natália VChammas RogerRodrigues Danielle BMorganti Ligia<p>Abstract</p> <p>Background</p> <p>Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.</p> <p>Results</p> <p>Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 10<sup>7 </sup>recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.</p> <p>Conclusions</p> <p>This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.</p> <p>Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.</p> http://www.biomedcentral.com/1472-6750/10/19
collection DOAJ
language English
format Article
sources DOAJ
author Balduino Keli N
Chura-Chambi Rosa M
da Costa Patrícia LN
Malavasi Natália V
Chammas Roger
Rodrigues Danielle B
Morganti Ligia
spellingShingle Balduino Keli N
Chura-Chambi Rosa M
da Costa Patrícia LN
Malavasi Natália V
Chammas Roger
Rodrigues Danielle B
Morganti Ligia
Anti-tumor therapy with macroencapsulated endostatin producer cells
BMC Biotechnology
author_facet Balduino Keli N
Chura-Chambi Rosa M
da Costa Patrícia LN
Malavasi Natália V
Chammas Roger
Rodrigues Danielle B
Morganti Ligia
author_sort Balduino Keli N
title Anti-tumor therapy with macroencapsulated endostatin producer cells
title_short Anti-tumor therapy with macroencapsulated endostatin producer cells
title_full Anti-tumor therapy with macroencapsulated endostatin producer cells
title_fullStr Anti-tumor therapy with macroencapsulated endostatin producer cells
title_full_unstemmed Anti-tumor therapy with macroencapsulated endostatin producer cells
title_sort anti-tumor therapy with macroencapsulated endostatin producer cells
publisher BMC
series BMC Biotechnology
issn 1472-6750
publishDate 2010-03-01
description <p>Abstract</p> <p>Background</p> <p>Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.</p> <p>Results</p> <p>Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 10<sup>7 </sup>recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.</p> <p>Conclusions</p> <p>This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.</p> <p>Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.</p>
url http://www.biomedcentral.com/1472-6750/10/19
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