Abstract LB-032: Magnetic 3D bioprinting for the identification of tumor-specific therapies from PDX-derived 3D cultures

Abstract

Abstract Great efforts have been undertaken in the field of cancer to develop clinically relevant pre-clinical models to permit the translation of research advances into agents that can improve patient outcomes. The use of 2D monolayer and 3D multicellular tumor spheroid cell culture systems has made this process remarkably costly and inefficient. This outcome is a result of discrepancies between simplified in-vitro 2D cell culture models used in drug screening platforms and the complex 3D tumor microenvironment targeted by these same drugs. Patient-derived xenograft (PDX), in which patient tumor tissue implanted into immune-deficient mice, provide improved models of human tumor biology relative to immortalized cancer cell lines. Such models offer possibilities for better preclinical testing of new therapies for the treatment of cancer. A drawback associated with the use of PDX systems is its requirement for immense resources and animals. Also, animal models have limited relevance as a platform for high throughput drug screening. To overcome such limitations, we applied magnetic 3D bioprinting to develop a PDX-derived ex-vivo tumor tissue platform for high-throughput drug screening. The PDX-derived tissue generated using magnetic 3D bioprinting mirrors the original PDX tumor in both tissue architecture and genetic signature. We confirm the predictive value of our screening template by demonstrating a similar response outcome between our model and a PDX mouse system generated from the same original tumor tissue and treated with the same panel of drugs. Utilizing an Inflammatory Breast Cancer (IBC) PDX system as our model system, we screened our ex-vivo tumor tissue template with the anti-cancer drug library and identified 7 lead candidates that had a stronger anti-tumor activity compared to the standard of care agents used to treat IBC patients in the clinics. Incorporating our ex-vivo tumor tissue high throughput screening platform as an early step in a PDX system will permit the identification of new and effective tumor-specific therapies at a time, cost, and resource efficient manner. Citation Format: Glauco Souza, Geoffrey Bartholomeusz. Magnetic 3D bioprinting for the identification of tumor-specific therapies from PDX-derived 3D cultures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-032.