Tumor anti-angiogenic gene therapy with microencapsulated recombinant CHO cells.
Microencapsulation of recombinant cells is a novel promising approach to tumor therapy in which therapeutic protein is sustainable and long-term delivered by microencapsulated cells. The semi-permeable membrane of microcapsule can protect cell from host's immune rejection, increase the chemical stability of therapeutic protein and circumvent the problems of toxicity, limited half-lives and variation in circulating levels. Endostatin, a potent and specific angiogenesis inhibitor, could suppress the growth of primary and metastatic lesions in multiple murine tumor models. In this paper, APA microcapsules with high strength kept intact over 35 days and recombinant CHO cells kept the rapid proliferation viability and the continuous endostatin-expression function. The study of tumor treatment showed that the implantation of microencapsulated recombinant CHO cells decreased the neovascularization of tumor tissue by 59.4% and inhibited the B16 melanoma growth by 77.4%. Twenty days after tumor cell injection, 80% of animals treated with microencapsulated CHO-endo cells were alive compared to only 50% of animals in either control or mock control groups. Therefore, continuous delivery of endostatin from microencapsulated recombinant cells represents a feasible approach to tumor therapy.
Zhang
Ying
Y
Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, P.R. China.
Wang
Wei
W
Zhou
Jing
J
Yu
Weiting
W
Zhang
Xulang
X
Guo
Xin
X
Ma
Xiaojun
X
D000818:Animals; D016466:CHO Cells; D002214:Capsules; D018914:Cells, Immobilized / Q000378:metabolism / Q000637:transplantation*; D006224:Cricetinae; D003412:Cricetulus; D043169:Endostatins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015316:Genetic Therapy; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008567:Membranes, Artificial; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013997:Time Factors
D002214:Capsules; D043169:Endostatins; D008567:Membranes, Artificial