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 107 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.