Solid tumors in vivo exhibit mass transport, complex cell-cell interactions, and oxygen gradients not well modeled in conventional adherent monolayer studies. Patient derived xenograft models excel in recapitulating some of the heterogeneity of the in vivo tumor microenvironment but are not tractable with real-time imaging and broad drug dose-response testing. Innovative 3D in vitro culture systems allow for screening of potential therapeutics in a pre-clinical setting, explore the dynamic tumor immune microenvironment in the presence of patient-matched immune cells, investigate pharmacological outcomes, and observe tumor evolution.
We have developed a 3D culture system integrating 3D printing in Liquid Like Solids (LLS) materials to enable the precise arrangement of highly detailed assemblies of cells and extra-cellular matrix components within a modular passive perfusion system.
Here we present the results of preliminary experiments designed to confirm the ability of our 3D bio-fabricated tumor models to recapitulate clinical behavior of the disease seen in patients. Using Western blotting and ELISA techniques we measured tumor dose responses to small molecule inhibitors targeting the EGFR, Ras, Raf, MEK, ERK pathway. Real-time imaging was performed in situ using confocal microscopy illustrating intra and inter-tumor heterogeneity, and autologous and allogenic T-cell responses of patient derived 3D microtissues.