Immunotherapy month: Receptor conflict—keeping cancer-killing T cells on-target using AIM Biotech’s organ-on-a-chip assays

This month on AIM’s Voices feed is dedicated to the fascinating research being done on adoptive T cell immunotherapy. Today, we’ll take a look at how scientists used AIM Biotech’s organ-on-a-chip technology to build on previous studies and refine this promising new technique to potentially fight cancer.

Conflicting receptors send T cells off-target

To engineer the body’s own immune system to attack tumors, scientists studying adoptive T cell immunotherapy modify healthy T cells to express proteins that let them recognize cancer cells. These proteins are called recombinant T cell receptors, or rTCR. In some cases, the expression of rTCR is affected by the expression of endogenous T cell receptors, or eTCR. The mix of rTCR and eTCR in the same T cell can cause it to attack healthy tissue instead of the intended tumor cells—clearly something to avoid when treating cancer!

Preece and coll implemented an extra modification on the T cells to prevent the expression of eTCR. The scientists took advantage of CRISPR, a technique that allows targeted, specific changes in DNA, and silenced the expression of eTCR on engineered T cells expressing rTCR. Later, both T cells—with or without eTCR expression—were tested on AIM Biotech’s three-dimensional organ-on-a-chip cell assays.

Testing the solution in an emulated tumor microenvironment

Scientists injected tumor cells in a collagen matrix in the central chamber of the chip. When T cells were added to the side medium channels, the team measured the number of T cells that migrated to the tumors and their capacity to kill the cancer cells.

In their observations, both types of the engineered T cells migrated similarly in proximity to the cancer cells—but looking at killing capacity, the T cells lacking eTCR were more than twice as effective than T cells expressing the eTCR proteins.

In this way, AIM Biotech’s organ-on-a-chip technology proved a valuable tool for efficiently gathering pre-clinical insights that would be impossible to model on a traditional simple assay.

More to follow next week with adoptive T cell immunotherapy and how AIM Biotech’s organ-on-a-chip tech facilitated these studies.

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.