(1013-B) An vascularized melanoma model for with unidirectional perfusion of circulating immune cells for Advancing Immune-Oncology Research

Abstract: Understanding the interactions between the tumor the vascular systems and circulating immune cells is crucial for elucidating mechanisms of immune cell recruitment in cancer and in exploring potential immunotherapeutic approaches. However, current in vitro models often lack the fidelity to replicate these intricate dynamics observed in vivo. The OrganoPlate Graft has been developed for perfusion of peripheral blood mononuclear cells (PBMCs) through a vascular bed with a melanoma monolayer (A375) to study aspects such as immune cell adhesion, extravasation and interaction with the tumor.
The OrganoPlate Graft comprises 48 chips per plate, each designed to simulate the conditions of vascular beds. The device achieves flow through passive levelling, utilizing gravity to induce a pressure drop and unidirectional flow across the vascular bed in both positive and negative inclines. This approach avoids the complications and potential artefacts introduced by external pump, reduces complexity, and increases the throughput with up to 16 plates (768 chips) served by each OrganoFlow rocker.
In experimental settings, formation of the vascular bed was seen to be consistent in plates and the introduction of the chemokine CXCL-12 led to the establishment of a gradient. Subsequently, PBMCs were observed to localize in clusters as a result of extravasation towards this gradient and the A375 monolayer. This behaviour is consistent with known chemotactic responses in more complex in vivo environments. A notable observation was the sustained activity of PBMCs within the system. Cells continued to perfuse through the vascular bed for up to three days after seeding.
In summary, the OrganoPlate Graft provides a platform for studying immune interactions in an immunocompetent vascular bed model. Its design and functionality allow for the exploration of immune cell behaviour in proximity to tumor cells, offering potential insights for immune-oncology research. The system's ability to mimic immune cell migration and extravasation in a controlled environment, and future potential to observe tumour killing makes it a valuable tool for advancing our understanding of immune-tumor interactions and may contribute to the development of novel immune-oncology therapeutic strategies.