The efficacy of alginate encapsulated CHO-K1 single chain-TRAIL producer cells in the treatment of brain tumors.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Kuijlen
Jos M A
JM
Department of Neurosurgery, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. jmakuijlen@nchir.umcg.nl
de Haan
Bart J
BJ
Helfrich
Wijnand
W
de Boer
Jan-Freark
JF
Samplonius
Douwe
D
Mooij
Jan Jakob A
JJ
de Vos
Paul
P
D000464:Alginates; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004339:Drug Compounding; D005260:Female; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D057127:Single-Chain Antibodies
D000464:Alginates; D006603:Hexuronic Acids; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C499789:scFvC54-sTRAIL fusion protein; D020723:Glucuronic Acid