Abstract A33: The implication of patient derived tumor cell (PDTC) tested/screened with novel microtube array membrane (MTAM)-based hollow fiber assay (HFA).
Authors: Wei Po-Li , Tseng Chia-Shiuan , Chen Chien-Chung , Chiu Chien-Jin , Hsiao George 
Published: March 2017

Background: Previously we have demonstrated the novel microtube array membrane (MTAM) can serves as an excellent substrate for a rapid, in vivo anti-cancer drug screening assay based on the hollow fiber assay (HFA), with higher cell-drug sensitivity, cell-host interaction, plus the clear angiogenesis, owing to its unique structural characteristics. In current study, the patient derived tumor cells (PDTC) were subjected to MTAM/X based screening platform. Patient derived colon cancer sample was treated and loaded into MTAM, studied first in cell growth and characterization, and later the cell toxicity by several representative cancer drugs, both in vitro and in vivo. The goal of this study is to explore the potential of utilizing MTAM/X with PDX for rapid, reliable, lower cost personalized anti-cancer drug selection platform.

Materials and Methods: Nano-porous PLLA MTAMs (npMTAM) were fabricated via a co-axial electrospinning and characterized morphologically first, then mechanical and permeation properties were determined. The nano-porous microstructure was also characterized by porosimeter. PTDC (colon cancer, 0.5 cm3) was obtained surgically and treated with enzyme-containing medium, homogenized before loaded into npMTAM at 105-106 cell per sample. The subcutaneous implantation of these MTAMs were conducted with 4 MTAMs per model (BALB/c) one day before the drug treatment. Regiments used according to the recommended dosage were cisplatin, 5 FU and Erbitux. In vitro and in vivo PDTC growth within MTAM were determined via MTT assay. The in vivo drug cytotoxicity towards PDTC was then determined by MTT in a 9-day period, in the meantime, the supportive results of angiogenesis was characterized via imaging process.

Results: Nano-porous PLLA MTAMs were successfully prepared with a tube wall thickness of 2-3 microns and pore size of 100-200 nm. PDTC (colon cancer) was loaded into npMTAM within 2 hours after surgical collection. The in vitro and in vivo growth of PDTC in npMTAM was observed clearly in a two weeks period. Upon the administration of 5 FU, Cisplatin and Erbitux to the test model, cell growth was altered, however in different fashion. 5FU show early cell cytotoxicity, however, loss its inhibition capability afterwards. Erbitux showed no sign of inhibition. Finally greatest inhibition of this particular patient tumor was found with cisplatin. Extent of angiogenesis was found to be in consist with MTT data. The overall time needed to generate the final results is within 2 weeks.

Conclusions: Testing PDTC in vivo within npMTAM based assay (PDXiMTAM), we demonstrated the feasibility of in vivo personalized cancer drug selection platform can be achieved in a reasonable time periods of 2 weeks. Selection from a group of four regiments, cisplatin demonstrated its highest cytotoxicity towards this specific tumor. This will be a very practical assay in clinical setting to identify most effective drug at personal level. Our results therefore suggest that such assay could be further developed in timely treatment selection. A double blind, cohort clinical trial of 60 patients with colon cancer is currently ongoing to validate PDXiMTAM.

Citation Format: Po-Li Wei, Chia-Shiuan Tseng, Chien-Chung Chen, Chien-Jin Chiu, George Hsiao. The implication of patient derived tumor cell (PDTC) tested/screened with novel microtube array membrane (MTAM)-based hollow fiber assay (HFA).. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A33.