Abstract 3848: Cryopreserved, viable and architecturally intact lung tissue from patients as a model to study drug therapies.

Abstract

Abstract RATIONALE: Surgery, chemotherapy and radiation have not appreciably improved lung cancer patient survival rates over the past 20 years. Preclinical anti-tumor efficacy testing models could be improved by being rapid, reliable and capable of demonstrating tumor responses to dosing (concentration/timing) and drug interactions, while accounting for inter-patient variation. High-throughput, 3D in vitro systems hold promise as such therapeutic models, but linking these models to clinical responses in patients has been a dilemma. METHODS: We developed a lung tissue cryopreservation/banking method that optimizes cell viability and maintains tissue architecture after thawing. This method involves the expansion-perfusion of fresh patient lung tissue samples with non-toxic cryoprotectant solutions, followed by controlled-rate freezing of samples. RESULTS: We used this method to cryopreserve lung tissues from multiple patients. Although inter-patient variability in lung tissue compliance was anticipated, a wide range of expansion volumes can be tolerated without architectural damage. In contrast, tissue integrity was more sensitive to variations in expansion-perfusion rates (as gauged by lymphatic expansion/tearing). Cryosubstitution demonstrated that crystal formation varies with cryoprotectant cocktail and region within the lung, but can be virtually eliminated under certain conditions. From thawed lung tissues, we have 1) isolated and expanded viable lung cell types; 2) isolated decellularized extracellular components; and, 3) reconstituted intact lung tissue with fluorescent-tagged lung tumor cells. We performed patient surgeries/preservations individually, thawing, processing and analysis of lung tissue from multiple patients was performed simultaneously. CONCLUSION: Cancer cell drug responses are being compared in lung tissues ex vivo versus on standard monolayer culture using advanced proteo-/lipidomic mapping techniques (including MALDI MS and DIGE). Comparing multiple patient-specific lung tissues simultaneously should afford patient population stratification based on molecular profiles and achieve more rapid methods for determining personalized clinical treatment regiments. Citation Format: Demetri D. Spyropoulos, Chadrick E. Denlinger, Ellen C. Riemer, Danforth A. Newton, E. Ellen Jones, Richard R. Drake, John E. Baatz. Cryopreserved, viable and architecturally intact lung tissue from patients as a model to study drug therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3848. doi:10.1158/1538-7445.AM2013-3848