Immunotherapy month: The immune system workaround—suppressing immune checkpoint expression to attack tumors with T cells in AIM Biotech’s organ-on-a-chip

You learned last week how AIM Biotech’s organ-on-a-chip is the perfect model for studying T cell migration to a 3D tumor while examining adoptive T cell immunotherapy. Today, we’ll discuss how scientists used the same technology to discover a major improvement to the therapy.

A new obstacle: immune checkpoints

Although the discovery that the body’s T cells can be engineered to attack tumors is a major find, the technique faced a major obstacle: some immune checkpoints can stop engineered T cells from attacking tumor cells altogether. The PD-1 immune checkpoint protein, for example, eliminates T cells’ capability to attack cancer cells if activated. Otano and co-workers show us how knocking down the expression of PD-1 protein improves T cell efficacy to kill tumor cells.

Exploring a solution with AIM organ-on-a-chip tech

To counter this problem, the scientists engineered human T cells from healthy donors to knock down the expression of PD-1 protein, creating what we’ll refer to as PD-1 KO T cells. Then, they used AIM Biotech’s organ-on-a-chip to generate 3D tumors in the central chamber of the chip, where the hydrogel filling serves as a matrix for the tumors. Once the 3D tumors formed, they injected human engineered T cells, either with or without PD-1 expression, on the side medium channels. They measured the migration of the two T cell types and their ability for killing the cancer cells. After performing these experiments, the scientist discovered that PD-1 KO T cells performed better than regular engineered T cells. This discovery is a huge step for adoptive T cell immunotherapy, overcoming a major barrier to increased efficacy in eliminating tumor cells using T cells.

Life—including science—is full of ups and downs

In spite of this success, the scientists now ran into a new problem: while PD-1 KO T cells are remarkably effective, they are only active for a short period of time—but our story doesn’t end here. Stay tuned that next week you’ll discover how following studies came up with a solution to keep T cell ability for a longer period of time in order to make better use of this discovery. And remember—this fascinating story is just one example of how AIM Biotech’s organ-on-a-chip is helping scientists gather more actionable preclinical data in their search for new cancer therapies.

Gathering more predictive, human-relevant data like this is what AIM’s unique human-on-a-chip tech is all about. Want to discuss how this researcher-friendly tech can transform your research, too? Use the chat bubble on the bottom right corner of this page, and we’ll reach out to you—or check out our Contact Us page. Also be sure to look at how our contract research services can help streamline your workflow.