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Anti-tumor therapy with macroencapsulated endostatin producer cells
BACKGROUND: 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. End...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845092/ https://www.ncbi.nlm.nih.gov/pubmed/20196841 http://dx.doi.org/10.1186/1472-6750-10-19 |
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author | Rodrigues, Danielle B Chammas, Roger Malavasi, Natália V da Costa, Patrícia LN Chura-Chambi, Rosa M Balduino, Keli N Morganti, Ligia |
author_facet | Rodrigues, Danielle B Chammas, Roger Malavasi, Natália V da Costa, Patrícia LN Chura-Chambi, Rosa M Balduino, Keli N Morganti, Ligia |
author_sort | Rodrigues, Danielle B |
collection | PubMed |
description | BACKGROUND: 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. RESULTS: 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(7 )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. CONCLUSIONS: This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors. Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors. |
format | Text |
id | pubmed-2845092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28450922010-03-26 Anti-tumor therapy with macroencapsulated endostatin producer cells Rodrigues, Danielle B Chammas, Roger Malavasi, Natália V da Costa, Patrícia LN Chura-Chambi, Rosa M Balduino, Keli N Morganti, Ligia BMC Biotechnol Research article BACKGROUND: 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. RESULTS: 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(7 )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. CONCLUSIONS: This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors. Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors. BioMed Central 2010-03-02 /pmc/articles/PMC2845092/ /pubmed/20196841 http://dx.doi.org/10.1186/1472-6750-10-19 Text en Copyright ©2010 Rodrigues et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research article Rodrigues, Danielle B Chammas, Roger Malavasi, Natália V da Costa, Patrícia LN Chura-Chambi, Rosa M Balduino, Keli N Morganti, Ligia Anti-tumor therapy with macroencapsulated endostatin producer cells |
title | 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_short | Anti-tumor therapy with macroencapsulated endostatin producer cells |
title_sort | anti-tumor therapy with macroencapsulated endostatin producer cells |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845092/ https://www.ncbi.nlm.nih.gov/pubmed/20196841 http://dx.doi.org/10.1186/1472-6750-10-19 |
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