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Modification of Hemodialysis Membranes for Efficient Circulating Tumor Cell Capture for Cancer Therapy
Authors:Gabor Jarvas  Dora Szerenyi  Jozsef Tovari  Laszlo Takacs  Andras Guttman
Institution:1.Research Institute of Biomolecular and Chemical Engineering, Faculty of Engineering, University of Pannonia, 8200 Veszprem, Hungary; (G.J.); (D.S.);2.CAPTEC Medical Ltd., 1124 Budapest, Hungary;3.Department of Experimental Pharmacology, National Institute of Oncology, 1122 Budapest, Hungary;4.Laboratory of Monoclonal Antibody Proteomics, Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary;
Abstract:Background: It is well known that more than 90% of cancer deaths are due to metastases. However, the entire tumorigenesis process is not fully understood, and it is evident that cells spreading from the primary tumor play a key role in initiating the metastatic process. Tumor proliferation and invasion also elevate the concentration of regular and irregular metabolites in the serum, which may alter the normal function of the entire human homeostasis and possibly causes cancer metabolism syndrome, also referred to as cachexia. Methods: We report on the modification of commercially available hemodialysis membranes to selectively capture circulating tumor cells from the blood stream by means of immobilized human anti-EpCAM antibodies on the inner surface of the fibers. All critical steps are described that required in situ addition of the immuno-affinity feature to hemodialyzer cartridges in order to capture EpCAM positive circulating tumor cells, which represents ~80% of cancer cell types. Results: The cell capture efficiency of the suggested technology was demonstrated by spiking HCT116 cancer cells both into buffer solution and whole blood and run through on the modified cartridge. Flow cytometry was used to quantitatively evaluate the cell clearance performance of the approach. Conclusions: The suggested modification has no significant effect on the porous structure of the hemodialysis membranes; it keeps its cytokine removal capability, addressing cachexia simultaneously with CTC removal.
Keywords:hemodialysis  circulating tumor cell  capture  therapy
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