Immunotherapy month: Tracking T cell migration for use in immunotherapy using a 3D organs-on-a-chip

This month we are exploring the details of adoptive T cell Immunotherapy and how AIM Biotech’s technology facilitated the development of this relevant technique for cancer treatment.

In adoptive T cell immunotherapy, the body’s immune T cells are engineered to attack cancer cells. To this end, these engineered T cells must be able to migrate from the blood to the tumor in question in order to kill the cancer cells. In 2017, Andrea Pavesi and collaborators studied the importance of different microenvironment conditions on the migration of T cells to hepatic tumors. By harnessing AIM Biotech’s technology, they built hepatic 3D tumors on the central chamber of AIM’s organ-on-a-chip containing a collagen matrix. Later, they injected engineered T cells on the side channels of the chip and measured their migration capacity to the tumors and their ability to kill the targeted cells. You can see this process captured in real time in the adjacent video! Exposing the 3D tumors to different microenvironment conditions, they found that these T cells are more effective when oxygen concentration is high. Also, the presence of inflammatory cytokines IFN-γ and TNF-α, normally present on cancer conditions, helped the performance of T cells to kill tumor cells.

Solving the gravity problem: how AIM’s 3D assays achieved more predictive results

Importantly, the scientists emphasized the relevance of working on a 3D environment, comparing their results on the AIM’s chip with a conventional 2D system on a Petri dish. They saw, for example, that oxygen dependence was only relevant on 3D chips, highlighting the importance of performing these experiments on the closest conditions to an in vivo model. These differences were caused by the different driving forces that govern in each dispositive. On the Petri dish, T cells are sinking in fluid by gravity, so they always reach cancer cells. Instead, on AIM’s chip, T cells migrate by chemotaxis signals to the central chamber of the chip. Only T cells that recognize cancer cells’ signals reach the center of the chamber. Removing gravity as a variable better mimics reality in an animal body, demonstrating the efficacy AIM Biotech’s organ-on-a-chip can have in preclinical studies.

More to follow next week with AIM’s organ-on-a-chip and adoptive T cell immunotherapy!