Nature-inspired 3D scaffolds to improve t-cell culturing environments for adoptive cell transfer cancer immunotherapy Lucy Todd, Matthew Chin, Marc-Olivier Coppens UCL, United Kingdom Centre for Nature Inspired Engineering & Department of Chemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom Body of abstract There are very few people today who have not been affected by a cancer diagnosis either personally or through a loved one. Cancer can often appear as a growing, undefeatable threat. However, the portfolio of life saving treatments continue to expand with ever increasing success rates. One of the most promising cancer immunotherapy treatments on the market and in research today is the Chimeric Antigen Receptor (CAR) T-cell Adoptive Cell Transfer (ACT). During this treatment, a patient’s own T-cells areextracted, proliferated, and activated ex vivo, genetically engineered to attack the specific tumour cells and then re-infused back into the patient. One of the main challenges with this treatment is the large number of activated T-cells required to proliferate. 1 Currently, ex vivo T-cell culturing environments tend to be quasi-2D, therefore, they neglect to facilitate the 3D mechanical and physical interactions required for efficient T-cell proliferation and activation. 2 By applying the nature-inspired chemical engineering (NICE) framework developed at UCL, over 9000 unique, lymph node inspired, 3D T-cell culturing scaffolds have been designed. 3, 4 Ongoing research addresses two fundamental software projections, with the goal to improve the design, efficiency, and scalability of these nature-inspired, 3D T-cell culturing environments. Firstly, to design a wide variety of 3D scaffolds to test as T-cell culturing environments and secondly, to systematically examine how the geometric and topological parameters of those environments affect the T-cells. To design the scaffolds, a streamlined computational pipeline has been constructed to both build the scaffolds and calculate 15 geometric and topological parameters (such as the porosity and surface area). 5 Currently, over 9000 3D scaffolds have been processed with adaptability functions programmed into the pipeline for future 3D scaffolds designs. Secondly, to design a systemic analysis platform, a novel web-based networking software has been designed. This software, applied to efficiently analyze and process the various scaffolds designed, integrates both the geometrical characteristics of the scaffolds and biophysical aspects related to the cells (such as a biophysical readout). This software efficiently processed the 9000+ scaffolds, designing multiple networks which informed the scaffolds selected for wet lab testing. With this knowledge we aim to design improved T-cell culturing environments that can be applied within cancer therapy to make CAR-ACT a more affordable and efficient cancer treatment. References 1. Jin, Z.; et al. Engineering the Fate and Function of Human T-Cells via 3D Bioprinting. Biofabrication 2023 , 13 (3). 2. Jensen, C.; Teng, Y. Is It Time to Start Transitioning From 2D to 3D Cell Culture? Frontiers in Molecular Biosciences 2020 , 7, 33. 3. Coppens, M.-O. Nature-Inspired Chemical Engineering for Process Intensification. Annual Review of Chemical and Biomolecular Engineering. 2023 , 12 (1), 187–215. 4. Chin, M. H. W.; et al. Rethinking Cancer Immunotherapy by Embracing and Engineering Complexity. Trends Biotechnology. 2020 , 38 (10),1054–1065. 5. Todd, L.; Chin, M. H. W.; Coppens, M.-O. A Computational Pipeline to Optimize 3D Scaffolds for Cancer Immunotherapy.
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