OBJECT: Patients with astrocytic tumors in the central nervous system (CNS) have low survival rates despite surgery and radiotherapy. Innovative therapies and strategies must be developed to prolong survival of these patients. The alginate microencapsulation method, used to continuously release a certain cytotoxic agent in the vicinity of the tumor, is such a novel therapeutic strategy. The biological functionality of the apoptosis inducing scFv425:sTRAIL protein, which was released through the microencapsulation method, was studied in vitro. Analysis of the intracerebral biocompatibility of alginate capsules was performed by implantation of empty alginate capsules in the brain of mice. METHOD: Chinese Hamster Ovary cells (CHO-K1) were recombinantly engineered to produce the single chain anti-EGFR-sTRAIL protein (scFv425:sTRAIL). The CHO-K1 producer cells were encapsulated in an alginate capsule with a semi-permeable membrane through which the scFv425:sTRAIL protein could be released. RESULTS: In vitro studies show maintained biological functionality of the released scFv425:sTRAIL protein. There was no immunological tissue response detectable after intracerebral implantation of the alginate capsules in mice brains. CONCLUSION: Biological functionality of the produced scFv425:sTRAIL protein is maintained and intracerebral biocompatibility of the capsules is warranted. Alginate encapsulation of CHO-K1--scFv425:sTRAIL--producer cells and subsequently their intracerebral implantation is technically feasible. This study justifies further in vivo experiments.
OBJECT: Patients with astrocytic tumors in the central nervous system (CNS) have low survival rates despite surgery and radiotherapy. Innovative therapies and strategies must be developed to prolong survival of these patients. The alginate microencapsulation method, used to continuously release a certain cytotoxic agent in the vicinity of the tumor, is such a novel therapeutic strategy. The biological functionality of the apoptosis inducing scFv425:sTRAIL protein, which was released through the microencapsulation method, was studied in vitro. Analysis of the intracerebral biocompatibility of alginate capsules was performed by implantation of empty alginate capsules in the brain of mice. METHOD:Chinese Hamster Ovary cells (CHO-K1) were recombinantly engineered to produce the single chain anti-EGFR-sTRAIL protein (scFv425:sTRAIL). The CHO-K1 producer cells were encapsulated in an alginate capsule with a semi-permeable membrane through which the scFv425:sTRAIL protein could be released. RESULTS: In vitro studies show maintained biological functionality of the released scFv425:sTRAIL protein. There was no immunological tissue response detectable after intracerebral implantation of the alginate capsules in mice brains. CONCLUSION: Biological functionality of the produced scFv425:sTRAIL protein is maintained and intracerebral biocompatibility of the capsules is warranted. Alginate encapsulation of CHO-K1--scFv425:sTRAIL--producer cells and subsequently their intracerebral implantation is technically feasible. This study justifies further in vivo experiments.
Authors: W Roth; S Isenmann; U Naumann; S Kügler; M Bähr; J Dichgans; A Ashkenazi; M Weller Journal: Biochem Biophys Res Commun Date: 1999-11-19 Impact factor: 3.575
Authors: A M Chinnaiyan; U Prasad; S Shankar; D A Hamstra; M Shanaiah; T L Chenevert; B D Ross; A Rehemtulla Journal: Proc Natl Acad Sci U S A Date: 2000-02-15 Impact factor: 11.205
Authors: D F Emerich; S R Winn; P M Hantraye; M Peschanski; E Y Chen; Y Chu; P McDermott; E E Baetge; J H Kordower Journal: Nature Date: 1997-03-27 Impact factor: 49.962