Designing Vascular Geometries in 3D Bioprinted Models for Immuno-oncology

Cancer is a global challenge. Addressing this, the EU Mission on Cancer aims to improve the lives of >3 million people by 2030. To achieve this goal requires not only new treatments, but also new in vitro platforms to study how their efficacy can be maximised. Cancer immunotherapy has been a promising treatment for certain haematological cancers, but is encountering tremendous challenges when used for solid cancers. One of the main reasons is that tumours are often protected by an immunosuppressive microenvironment that impedes the delivery and infiltration of immune cells, such as T cells. Specifically, the tumour vasculature is both structurally and functionally abnormal, which interrupts the transport of therapeutic T cells to tumour sites. This project (VASPRINT) will fabricate tumour models containing different vascular architectures. To this end, VASPRINT will combine top-down bioprinting with bottom-up self-assembly methods to create hierarchical vascular networks. VASPRINT will employ analytical tools from graph theory and fractal geometry to gain a quantitative understanding of the vascular structures. The engineered tissue model will be used to address a key question: how does tumour vascular geometry influence T cell trafficking? Despite advancements, the specific effects of vascular geometry on T cell trafficking remain poorly understood. This proposal includes learning bioprinting from the Associated Partner (Harvard University), as well as fractal analysis and modelling from the Beneficiary (University College London). In return, the Researcher will contribute his expertise in the algorithmic design of biomaterial structures (outgoing phase) and developing advanced tumour models for T cell therapy research (return phase). This project aims to advance the scientific understanding of tumour vasculature in the context of immuno-oncology, generating useful insights for therapy development, ultimately contributing to the EU Mission on Cancer.