One of the major challenges in developing successful cancer therapies is the inhibitory effect caused by immune checkpoint resistance, normally including the PD-1 checkpoint protein in T cells that we’ve highlighted in previous posts. As a result, in vitro models that faithfully recreate the microphysiology of immune checkpoint blockade in humans are critical for next-generation cancer treatments.
Over the next few weeks, we’ll explore some publications that demonstrate the use of AIM Biotech idenTx organ-on-a-chip models to study immune checkpoint blockade.
Creating tumor models on idenTx chips from mouse and human biopsies
Work from the Dana-Farber Cancer Institute, published in Cancer Discovery in 2018, described the use of idenTx chips to create an ex vivo 3D tissue culture model that maintains the tumor microenvironment and simulates the response to immune checkpoint blockade seen in vivo.
Jenkins and collaborators used a variety of mouse and human tumor biopsies as starting samples. From these biopsies, they created spheroids that were later mixed with collagen and injected into the central chamber of the idenTx chip. They showed that the tumor/immune cell intermixture in the spheroids was preserved within the chip in both mouse and human 3D tissue models.
Assaying anti-PD-1 treatment efficacy from mouse biopsies using idenTx chips.
The authors verified that the key characteristics of PD-1 blockade were maintained in the idenTx organ-on-a-chip model. For that, they used 3 different mouse cancer models: one that is resistant to anti-PD-1 treatment (B16F10), one that is known to respond to anti-PD-1 therapy (MC38), and a third one that is semi-sensitive to the same treatment (CT26). After applying the anti-PD-1 monoclonal antibody to the chip to mimic the immune checkpoint blockade therapy, they found that the efficacy of anti-PD-1 therapy on killing cancer cells was proportional to the in vivo anti-PD-1 sensitivity: B16F10 < CT26 < MC38. This result demonstrates that the anti-PD-1 sensitivity observed in mice in vivo is conserved in the 3D tissue model on idenTx chip.
Assaying early immune response on idenTx chip from patient biopsies
The scientists also confirmed the efficacy of a patient-derived model to anti PD-1 treatment by measuring early immune activation molecules. For that, three days after anti-PD-1 injection on the chip, they measured the production of different immune proteins, finding an increase in the cytokine CCL19 and chemokine CXL13 in 23 of the 28 patient-derived spheroids analyzed. Later, they measured CCL19 and CXL13 in vivo in patients with melanoma treated with anti-PD-1 therapy. They found that, in effect, biopsies from these patients
contained an elevated production of CCL19 and CX13, confirming the use of idenTx chip as an excellent model for studying immune checkpoint blockade therapy.
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.
*Ex vivo profiling of PD-1 Blockade Using Organotypic Tumor Spheroids. Jenkins RW, et al. Cancer Discov. 2018 Feb;8(2):196-215. doi: 10.1158/2159-8290.CD-17-0833. Epub 2017 Nov 3. PMID: 29101162; PMCID: PMC5809290.