Abstract
Abstract Intratumoral electroporation of proinflammatory cytokine-encoding plasmid DNA promotes innate and adaptive immune responses that correlate with abscopal effects. The conditions selected to electroporate tumors are typically fixed parameters optimized in preclinical tumor models. These conditions have little translatability to clinically relevant tumors, as idealized models fail to capture the variability encountered in clinical tumors. Variables that affect treatment outcome include tumor size, degree of vascularization, fibrosis, and necrosis. These variables can result in sub-optimal gene transfer and variable therapeutic outcomes. To address the need to advance the practice of electroporation, a feedback controlled electroporation generator has been developed, which is capable of assessing the electrophysiological properties of tissue in real-time. Determination of these properties is accomplished by electrochemical impedance spectroscopy and model parameter estimation. Model parameters that estimate membrane integrity are used to adjust electroporation parameters for each applied pulse and stop the process when optimum gene transfer conditions are identified. Studies performed in syngeneic colon carcinoma tumors (MC38) and spontaneous mammary tumors (MMTV-PyVT) have demonstrated feedback-based electroporation is capable of achieving maximum expression of reporter genes with minimal collateral cell death. These findings represent an unprecedented advancement to the practice of gene electro-transfer, as retaining the viability of transfected cells is paramount to treatment success. Citation Format: Douglas W. Brown, Arya J. Bahrami, David A. Canton, Yi Xu, Gavin Y. Tse, Jean S. Campbell, Robert H. Pierce, Richard J. Connolly. Feedback optimized gene electrotransfer for immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B32.
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